NEONATAL SURGERY - 1976

2. SPECIAL SECTIONS

11. Tumors

   The decline in overall infant mortality recorded in recent years has been accompanied by a relative and absolute increase in mortality from malignant diseases (Miller, 1968). According to World Health Organization data (Dargeon, 1960), malignant neoplasms accounted for 9.8% of all deaths in children aged 1 to 4 years. Tumors in the perinatal period are observed in approximately 0.25% of all autopsies of fetuses and newborns. This figure does not include benign tumors, which occur more frequently in children than malignant ones.

Fraumeni and Miller (1969) report that out of 21,929 children who died in the USA between 1960 and 1964 from malignant tumors, 130 (0.6%) were under 28 days of age. Among 9,619 deaths from malignant neoplasms in children under 5 years of age, infants under 28 days accounted for 1.4%. Mortality from tumors in this age group was 6.24 per 1 million live births, including 2.11 from leukemia, 1.3 from neuroblastoma, 0.34 from Brain Tumors, 0.43 from Wilms' Tumor, 0.48 from primary Liver Cancer, 0.43 from teratoma, and 1.16 from other tumors. Congenital Malformations were noted in 12 out of the 130 children.

Shanklin and Sotelo-Avila (1969), performing autopsies on 471 neonatal corpses, discovered tumors in 5 cases (1:94); these included three neuroblastomas and two Wilms' tumors. In all 5 cases, the tumors were associated with congenital malformations, most frequently of The Heart.

The majority of children are admitted to specialized pediatric oncology centers between the ages of 2 and 5 years, as neuroblastomas and nephroblastomas (Wilms' tumors), which are common in children, are most frequently diagnosed during this period. A review of the disease history in these patients suggests that onset dates back to the neonatal period. For instance, an analysis of 306 cases of Wilms' tumor in children under one year of age allowed for three groups to be distinguished: 1) with a "definitely" prenatal onset of the tumor, detected within the first 14 days of life (62 cases, or 20.4%); 2) with a "probably" prenatal onset, discovered between 3 and 12 weeks of life (48 cases, or 15.2%); 3) with a "possibly" prenatal onset, identified between 4 and 12 months of life (199 cases, or 64.4%) (Bachmann, Kroll, 1969).

We believe that the upper limit for a "possible" prenatal origin of a tumor can be extended up to 5 years, since children aged 3 to 5 years are often admitted with advanced Stages of the disease (up to 70–80%). Given the prolonged latent course of the tumor, its onset can be attributed to the perinatal period with a high degree of certainty.

Detecting tumors in children at an early stage yields more encouraging results. For example, children with Wilms' tumor operated on under the age of 1 year have a survival rate of over 80%, and under 6 months, 100%. At the same time, the survival rate of children treated after one year of age does not exceed 25–30%, even by the most optimistic estimates.

Bolande (1971) points to the more benign course of the tumor process and a favorable prognosis in newborns, reporting cases of spontaneous regression of neuroblastoma, retinoblastoma, and even leukemia.

The author believes that elucidating the reasons for the relatively favorable course of neoplasms in these infants may shed light on certain issues in General Oncology.

One of the reasons for the increase in malignant tumors in children in recent years is the rise in radiation exposure. Thus, Stewart and Kneale (1968) noted that the incidence of malignant tumors was 0.95% in children of healthy mothers, 1.48% in children born to mothers exposed to radiation once, and 2.24% in those whose mothers were irradiated more than 5 times. Statistical calculations of the probability of developing malignant tumors following fetal irradiation at a dose of 1 rad showed an average increase of 572 cases per 1 million live births above the statistical average. Radiation exposure to the fetus During the first 3 months of Pregnancy is particularly dangerous. The same authors (1970) present the age distribution of 5,802 children with tumors and 1,045 children who underwent X-ray irradiation in utero and subsequently developed neoplasms. They compared the actual and statistically expected numbers of hematopoietic and solid tumor malignancies in both groups, as well as the age distribution of the patients (accounting only for those born between 1943 and 1965 and who died between 1953 and 1965 at under 10 years of age). Among those exposed to intrauterine irradiation, the "excess" of cases amounted to 423, of which only 20 could not be linked to radiation.

A number of authors associate The Development of tumors in children with malformations. Dargeon (1960) and Berry (1970), in order to determine the frequency of malformations in children with malignant tumors, analyzed data on 96 children with teratomas, 103 with nephroblastomas, 144 with neuroblastomas, and 40 with hepatoblastomas. The authors found no significant correlation between malformations and tumors.

Miller (1966) provides an epidemiological evaluation of the relationship between malignant tumors and congenital defects. He conditionally divides childhood tumors into three groups. The first group includes leukemia, Wilms' tumor, liver and Adrenal Cancer, and neuroblastoma. These tumors are frequently associated with various malformations. Lymphocytic Leukemia is characteristically associated with Down syndrome, while the remaining tumors in this group (except neuroblastoma) are associated with hemihypertrophy. Wilms' tumor is frequently accompanied by aniridia (Congenital absence of the iris). The second group comprises brain tumors. They are associated with Central Nervous system malformations (a certain predisposition to gliomas is observed in patients with tuberous sclerosis and neurofibromatosis). The third group includes genital tumors, which also frequently occur concurrently with malformations. Lymphomas are associated with congenital agammaglobulinemia, and Bone tumors with multiple exostoses, enchondromas, and Osteogenesis Imperfecta.

Attempts to explain the fetal origin of a tumor via placental metastasis were considered unjustified until recently. Potter et al. (1970) found only 24 reports in world literature from 1866 to 1966 regarding metastasis of malignant tumors to the Placenta and fetus. Among these, melanoma was present in 11 pregnant women, breast cancer in 4, Stomach cancer in 2, Lung Cancer in 2, and lymphosarcoma, femoral Sarcoma, adrenal sarcoma, ovarian sarcoma, and Ethmoid bone sarcoma in 1 woman each. Of the 8 metastases to the fetus, 7 were observed in cases of melanoma and 1 in lymphosarcoma. According to the authors, placental metastases are remarkably rare, which may be explained by the existence of biological defense mechanisms. An interesting report was published by Anders, Frick, and Kindermann (1970). A girl born from a first pregnancy died on the 17th day of life from widespread neuroblastoma metastasis. The tumor originated in the right Adrenal gland, with metastases affecting The Liver and Lungs. The placenta was also involved. One year later, the mother was healthy. It is hypothesized that the tumor developed in the placenta due to the transplacental transfer of tumor Cells from the infant.

We observed a girl who was born with a melanoma of the right thigh. Several months after childbirth, the mother died As a result of widespread metastasis of a melanoma also located on the right thigh.

Rothman (1973) presents data on 35 cases of malignant neoplasms in pregnant women. Almost all of these patients experienced rapid tumor dissemination and died. Autopsies revealed malignant involvement of the placenta or fetus.

Placental involvement was found in 13 out of 28 examined specimens. Of the 35 newborns in the published observations, 8 died from malignant dissemination, 2 from the spontaneous development of a tumor, and 1 child had a malignant metastasis. Sixteen children showed no signs of neoplastic disease. The authors believe that cancer during pregnancy is not so rare, with the placenta and fetus being affected in the majority of cases.

In recent years, significance has been attributed to transplacental blastomagenesis. If animals are administered carcinogenic substances at specific stages of pregnancy, offspring frequently develop various tumors shortly thereafter.

In this regard, at the latest symposium on childhood cancer (1972), it was suggested that special attention be paid to The Use of various medications by pregnant women.

According to our data, tumors most frequently occur in children whose mothers are over 35 years of age.

All types of tumors are encountered in newborns (Table 20).

Class="center">Table 20. Frequency of various tumors in newborns (based on literature data for 1962–1972)

Table 20 does not reflect the true ratio of various tumors in children, since rarely observed malignant tumors are described much more frequently than commonly occurring benign ones.

Benign tumors

Hemangiomas. The most common tumors in newborns are hemangiomas, which in the majority of cases are already present at birth (Table 21).

Table 21. Time of detection of hemangiomas (according to G. A. Fedoreev, 1971)

Clinical presentation. Hemangiomas occur twice as often in girls. Their typical localization is the face and scalp (85%). The size of hemangiomas at birth varies significantly—from pinpoint lesions to those covering nearly half of the Skin surface, with both types presenting equal risks. Frequently, a pinpoint hemangioma begins to grow rapidly immediately after birth, resulting in a permanent cosmetic defect, especially when located on the face. Therefore, it is the pediatrician's duty to carefully examine the child's skin (particularly the face and scalp) right at birth and document any hemangioma to ensure the infant is closely monitored by a pediatric surgeon thereafter.

Simple hemangiomas are superficial, affect only the skin, and have well-defined margins.

Cavernous hemangiomas consist of Blood-filled spaces and involve not only the skin but also the underlying soft Tissues. In some cases, the skin may remain unaffected by the tumor and exhibit only a slight bluish tint, which should be considered during Diagnosis. Combined hemangiomas also occur.

Diagnosing cutaneous hemangiomas in newborns is generally straightforward. When compressed, a hemangioma pales; upon release of pressure, it refills with blood and becomes even brighter. When the infant cries, hemangiomas may increase in volume in certain cases. In 1940, Kasabach and Merritt first described a syndrome characterized by the rapid growth of a hemangioma combined with a bleeding tendency, thrombocytopenia, profuse intratumoral Hemorrhage, and diffuse petechiae. By 1970, 94 cases of this syndrome had been described in the literature (Martinis, 1970).

Cutaneous hemangiomas rarely pose a threat to life; however, they can lead to irreversible cosmetic defects or impair organ function (for example, Vision). Recent studies have established (G. A. Fedoreev, 1971) that spontaneous regression of simple angiomas can be expected in some patients. Spontaneous regression most frequently occurs in hemangiomas of the scalp and external genitalia. Regression typically takes place between the ages of 2 and 5 years.

Treatment. Numerous treatment Methods for hemangiomas have been proposed: excision, ligation, injection therapy, cryotherapy, electrocoagulation, and Radiation therapy. Each method has specific indications. Cryotherapy is the most frequently used approach, successfully curing up to 70% of flat cutaneous hemangiomas.

Some authors (Zarem, Edgerton, 1966) have achieved the resolution of cavernous hemangiomas using prednisolone therapy.

Lymphangioma. Lymphangiomas are most frequently localized in the neck and axillary regions. The floor of the Mouth is also commonly affected. Lymphangiomas are classified into simple, cavernous, cystic, and mixed types. The majority of lymphangiomas are detected at birth (G. V. Chistovich, A. P. Malinin, 1961). As a rule, the tumor grows slowly; rapid growth is observed only in rare instances (such as the combination of a lymphangioma with a hemangioma).

Clinical presentation. Lymphangiomas have an elastic consistency and are covered with normal skin. Less commonly, the overlying skin is bluish, sometimes translucent, and severely thinned. The margins of the tumor are usually poorly defined.

Differential diagnosis is carried out with cysts, in particular lateral neck cysts. Neck cysts have well-defined borders and are smaller in size. In doubtful cases, fine-needle aspiration biopsy is used.

The clinical course of lymphangiomas is generally favorable. In rare cases, complications arise as a result of tumor suppuration. In such instances, against the Background of a sharp deterioration in the child's condition, the tumor becomes painful, and the skin Temperature over it rises. Certain localizations of lymphangiomas (floor of the mouth, Tongue, Mediastinum) can lead to asphyxia.

Treatment. Surgical intervention is performed once the diagnosis is established. The Need for emergency Surgical treatment may arise in the event of complications. If there are absolute contraindications to surgery, aspiration of the lymphangioma may be performed to reduce its volume.

Fibromas, lipomas. The clinical course of these neoplasms is favorable. Treatment consists of surgery after one year of age. Pigmented tumors (naevus pigmentosus pilosus). Affected areas of skin in such patients vary in color intensity from yellow to dark brown. The skin surface may be smooth, rough, verrucous, or covered with Hair. The clinical course of pigmented tumors is favorable. Treatment is surgical. After Puberty, There is a real risk of malignant transformation.

Malignant tumors

Wilms' tumor (nephroblastoma, embryonic nephroma¹) is apparently congenital in all cases, although Wilms' tumor is extremely rarely detected directly in the embryo. According to Dargeon (1960), by 1966 only 42 reports on Wilms' tumor in fetuses had been published. Isolated cases of Wilms' tumor in newborns have been described.

¹ There are more than 50 names for this disease in the literature.

Some malignant Renal Tumors in newborns diagnosed as Wilms' tumors are of a different nature. Burkholder, Beach, and Hall (1970) note that in a number of cases, hamartomas with a mixed Structure similar to that of Wilms' tumors, but lacking malignant cells, are misclassified as nephroblastomas. In such cases, the prognosis is favorable.

Clinical presentation. A reliable sign of Wilms' tumor is Palpation of a mass in the abdomen. Therefore, during routine systematic abdominal palpation in newborns, attention must be paid to renal enlargement. Most often, this enlargement is not associated with malignant growth (hy-

dronephrosis, benign abdominal cysts). To rule out a tumor, excretory urography is sufficient in most cases. In extremely rare cases (with a non-functioning Kidney), aortography has to be employed.

The General condition of a newborn with Wilms' tumor is usually unaffected. No blood or urine abnormalities are observed. In the first six months after birth, the tumor rarely reaches a large size, remains consistently mobile, and does not invade the renal capsule. The latter circumstance allows for surgery that is ideal in terms of oncological radicalism.

Excretory urography makes it possible to detect a number of Direct and Indirect signs of Wilms' tumor, manifesting as changes in renal contours, less commonly absence of renal function, and various deformations and disruptions of the normal pelvicalyceal pattern up to its complete disappearance.

Treatment. Combined treatment is used for Wilms' tumor in newborns and infants under 1 year of age. Following diagnosis, transperitoneal nephrectomy is performed with preliminary ligation of the renal vascular pedicle. The operation is relatively straightforward due to the mobility of the tumor. Postoperative radiation therapy is indicated (during the first days following surgery) at a dose ranging from 300 to 1000 rad, depending on the tumor size and the child's age. Medical treatment at this age is not administered in the absence of metastases (which, as a rule, do not occur in children under 1 year of age). We have successfully operated on children with Wilms' tumor at 1 to 2 months of age, observing no complications. With a properly executed surgery, the prognosis for infants under one year old is favorable.

Cases of bilateral Wilms' tumor localization in newborns have been described (Hou, Holman, 1961). We observed an infant in whom Wilms' tumor was detected at 2 months of age. The First stage involved a right-sided nephrectomy (the non-functioning, tumor-affected kidney was removed). Following a biopsy of the second kidney (which confirmed the diagnosis of Wilms' tumor), chrysomallin was introduced into its tissue. Seven years later, the child is virtually healthy.

Extremely rarely, other renal tumors (such as hamartoma) are encountered in newborns (Walker, Bichard, 1973; Fu, Kay, 1973).

Neuroblastoma — the most common malignant tumor in childhood, including the neonatal period. In our observations among 90 children with neuroblastomas, 19 were diagnosed before the age of one. At the same time, the diagnosis was established at the peak of the disease, often at an advanced stage of the process. In most cases, the basis for establishing the diagnosis was visually apparent Metastases in the cranial bones and the Orbit. Upon examining the Anamnesis, all of these tumors could undoubtedly be attributed to the neonatal period.

Becker, Schneider, and Kraska (1970) indicate that 70% of neuroblastomas are diagnosed before the age of five and consider these neoplasms to be congenital. Upon reviewing English-language literature up to 1956, the authors found descriptions of 56 cases of neuroblastoma diagnosed in the first month of life. They also reported 4 of their own observations.

Neuroblastomas include a number of tumors of neurogenic origin (sympathogoniomas, sympathoblastomas, immature ganglioneuromas).

Clinical presentation. Unlike Wilms' tumor, the general condition is compromised in newborns with neuroblastoma. The skin is pale, and birth weight is relatively low. Frequently, even during the neonatal period, a primarily generalized neuroblastoma with involvement of the bones, Bone Marrow, and liver can be encountered.

The tumor is most often located in the retroperitoneal space, in the adrenal region, or along the Sympathetic trunk. Intrathoracic localizations in newborns are rare (although they may go undetected due to a relatively benign course and are incidental radiographic findings at an older age).

Differential diagnosis is carried out between neuroblastoma and Wilms' tumor. Neuroblastoma is characterized by alterations in the child's general condition and elevated blood pressure. On radiographic examination, irregular foci of calcification in the center of the tumor are frequently found in neuroblastomas. Deformation of the pelvicalyceal system is insignificant; kidney displacement and deviation of the Ureters are more commonly noted.

In recent years, an important diagnostic test has emerged: the 24-hour urinary excretion of catecholamines, their precursors, and metabolites (vanillylmandelic and homovanillic acids). In children with neuroblastomas, a sharp increase in The excretion of these substances is observed in nearly 85% of cases, whereas this is not seen with other neoplasms. This research method is a valuable diagnostic test and provides objective data on the dynamics of the tumor process. Radical surgery leads to the rapid normalization of the urinary excretion of catecholamines and their metabolites.

Treatment of neuroblastoma is multimodal. The surgical method is the most reliable. Radical removal of the tumor leads to recovery in the majority of cases. Partial tumor removal (by piecemeal resection and debulking) is also possible and is performed in cases where radical removal is not feasible. In a number of cases, one must resort to combined surgical interventions (en bloc removal of the tumor with the kidney, Spleen, tail of the Pancreas, and liver resection). Surgical treatment is supplemented by radiation and drug therapy.

In generalized neuroblastoma, medical therapy is the primary treatment method. Vincristine and its combinations with other agents (cyclophosphamide and rubomycin C) are the most effective. According to recent data, 40% of patients with neuroblastoma under the age of one can be cured.

Retinoblastoma — a congenital malignant tumor of the retina, observed in 1 out of 34,000 newborns. Most authors emphasize the hereditary Nature of the disease, associated with a dominant Gene. Bilateral involvement is observed in 20–40% of cases.

Retinoblastoma can be suspected during the initial examination. Four stages are distinguished in the Development of the disease. In the first stage — the quiescent stage — careful examination can reveal signs characteristic of this tumor, namely amaurotic cat's eye reflex. In the second stage — the glaucoma stage — inflammatory phenomena appear; in the Third Stage — the infiltration stage — varying degrees of exophthalmos, invasion into the soft Tissues of the orbit, and destruction of its walls are observed. The final, Fourth Stage is the stage of metastasis to various Organs (brain, Lymph Nodes, lungs, Kidneys).

Treatment. Enucleation of the affected eye is performed, followed by radiation therapy. In recent years, radiation therapy alone has made it possible to achieve satisfactory results. Triethylenemelamine (TEM) has been used with success.

Rhabdomyosarcoma. Various malignant SOFT TISSUE TUMORS in newborns have been described (Kaufman and Stout [1965] have the largest number of observations). Vaginal rhabdomyosarcoma is the most frequently encountered. For instance, Ober, Smith, and Ronillard (1958) observed this tumor in 2 newborn girls (and successfully operated on them).

Clinical presentation. Vaginal rhabdomyosarcoma manifests as hemorrhagic vaginal discharge. Sometimes, prolapse of a polyp is detected. Himmel and Sugel (1967) present a rare report of a newborn rhabdomyosarcoma with multiple metastases. We observed vaginal rhabdomyosarcoma in a 5-month-old girl who was successfully operated on, underwent radiation and drug therapy, and is currently (4 years after detection) virtually healthy.

Cases of cardiac rhabdomyosarcoma in newborns are cited in the literature. M. G. Zholnerovsky (1957) reports on a girl who died on the 12th day after birth. A small tumor with clear margins, protruding into the lumen of the right ventricle, was found in the upper part of the interventricular septum. Rhabdomyosarcoma was established histologically.

Treatment for rhabdomyosarcomas is multimodal: surgical removal (if feasible) combined with radiation and drug therapy (Introduction/45.html">Antitumor Antibiotics).

Malignant mesenchymomas in newborns may be localized in the subcutaneous adipose tissue or limb Muscles, in the region of the ileum, or the rectum.

Fibrosarcoma is less common. It is located predominantly on the extremities. Treatment is surgical (amputation). With timely treatment, the prognosis is not hopeless. We observed a child who underwent amputation of the right arm at the age of 3 weeks. Six years later, he is virtually healthy.

Heick and Organ (1970) report a rare case of leiomyosarcoma in an 8-week-old infant, located in the scalp region. Four years after the operation, the boy is healthy.

Malignant soft tissue tumors in the region of the Urinary Bladder, tongue, Nose, auricle, etc., have been described. Localization of malignant tumors in the liver, pancreas, and other organs is also possible.

Carees, Drash, and Kenny (1969) reported the development of hepatoblastoma in 2 out of 4 children in a single family (at 11 weeks and 13 months). In one child, the tumor turned out to be inoperable, while the other underwent a lobectomy. Our department treated a 3-month-old infant with hepatocellular carcinoma of the liver originating from the left lobe. The child's mother noticed abdominal enlargement from the first days of life. The patient successfully underwent resection of the left lobe of the liver.

Fraumeni et al. (1968) observed an infant who was diagnosed with hypoglycemia 3 hours after birth, arising on the background of a pancreatic tumor.

Buist, Campbell et al. (1971) reported a case of islet Cell Adenoma of the pancreas. At 4 months of age, following medical therapy, the tumor was successfully excised and the child recovered.

Newborns may also present with tumors typically seen in adults. For instance, Borman prior to 1926 (cited by M. B. Kosyura, 1968) compiled 17 cases of Gastric Cancer in individuals under 20 years of age from the literature, including 2 in fetuses and 1 in a 5-week-old infant.

We observed a newborn who presented at birth with a neck mass that obstructed delivery. Within 2 weeks postpartum, the tumor grew to the size of the infant's HEAD and began to cause asphyxia. An urgent biopsy established the diagnosis of reticulum cell sarcoma. In another case, we observed reticulum cell sarcoma of the cervical Lymph Nodes in a 5-day-old infant. The tumor grew extremely rapidly, and despite intensive medical treatment, the patient died on day 25 from disease progression. There are isolated reports of Hodgkin's lymphoma, Bladder cancer, lung cancer, uterine cancer, Intestinal cancer, and other malignant neoplasms.

Thus, in the overwhelming majority of cases, newborns present with benign tumors that can cause not only cosmetic defects but also organ dysfunction. Pediatricians must always keep in mind the possibility of malignancies in newborns. If a neoplasm is suspected, the child should undergo a thorough evaluation and, if necessary, be transferred to a specialized medical facility.