Primary multiple tumors are neoplasms that occur simultaneously or after a certain period of time and are not metastases of each other. They can be benign or malignant, multicentrically located in one organ, occur in paired organs, localized within one system or several systems. They arise as a result of somatic mutations or hereditary genetic anomalies. They are diagnosed based on clinical symptoms, laboratory and instrumental studies. Treatment tactics are determined by the type, prevalence, localization and degree of malignancy of neoplasms.
Meaning
Primary multiple tumors are two or more neoplasias of various genesis, simultaneously or sequentially developed in one or more organs. In most cases, two neoplasms are diagnosed. Three nodes are found in 5-8% of patients. Cases of four or more neoplasias are extremely rare and are considered as casuistic. In recent decades, there has been a sharp increase in the number of primary multiple tumors, but the true frequency of their development is still the subject of research.
According to statistical data, primary multiple tumors are detected in 13% of patients with oncological diseases, however, some experts point out that this figure may be underestimated due to possible diagnostic errors (when determining an independent process, such as metastases of the primary neoplasm) and the death of some patients before the symptoms of a second neoplasia appear. Treatment of primary multiple tumors is carried out by oncologists, gastroenterologists, endocrinologists, mammologists, gynecologists and specialists in other fields of medicine (depending on the localization of neoplasms).
The first mention of multiple neoplasia is found in the writings of Avicenna, who described bilateral breast cancer more than a thousand years ago. In the XIX century, descriptions of primary multiple tumors became increasingly common in specialized literature. The most significant contribution to the definition of the concept and the study of this pathology was made by the German surgeon Billroth. In particular, he was the first to define such pathological conditions, referring to primary multiple tumors neoplasms of various structures, localized in different organs and giving their own metastases.
In the first half of the 20th century, the Biltot formulation was revised. Currently, primary multiple tumors are considered neoplasias, which can be located in one or in different organs. The main condition for assigning diseases to this category is the simultaneous or sequential appearance in the body of several centers of cell transformation independent of each other. The second and subsequent neoplasms should not occur as a result of contact spread, lymphogenic or hematogenous metastasis.
Causes
The direct cause of the development of solitary and primarily multiple tumors are genetic mutations caused by several factors. Taking into account the peculiarities of etiopathogenesis, three main types of neoplasia are distinguished: those that have arisen as a result of spontaneous somatic mutations, those formed as a result of induced somatic mutations, which are the result of inherited genetic mutations. It should be borne in mind that such a division is quite conditional. In practice, it is rather possible to single out the predominant cause of development, which is combined with other, less significant factors.
In primary multiple tumors, these mutations can be combined. Any combination is possible, for example, the first neoplasm develops spontaneously, the second – as a result of induction; the first is hereditary, the second is induced; both cancers have the same nature (heredity, the impact of exogenous factors), etc. At the same time, in patients with primary multiple tumors, there is a predominance of induced and hereditary mutations.
Among the most significant factors inducing the development of primary multiple tumors, smoking, living in unfavorable environmental zones, occupational hazards (contact with chemical mutagens in some industries, exceeding the established loads of radiologists), multiple X-ray examinations, radiation therapy and chemotherapy of previous oncological diseases are considered. The likelihood of primary multiple tumors also increases with nutritional disorders, immunodeficiency conditions, hormonal disorders and some endemic diseases.
The list of hereditary syndromes accompanied by obligate development or an increased likelihood of oncological lesions includes more than 100 diseases. Initially, multiple tumors develop or may develop with a third of such diseases. The most well-known syndromes are MEN-1, MEN-2 and MEN-3, in which multiple endocrine neoplasias are detected. In addition, primary multiple tumors can be diagnosed with Lynch syndrome, Gardner syndrome, Hippel-Lindau disease, Peitz-Jaegers syndrome and others.
Classification
There are several classifications created at different stages of the study of this pathology. Modern specialists usually use the Baby’s classification, developed in 1974. According to this classification, the following types of primary multiple tumors are distinguished:
- Taking into account the combinations: all neoplasms are benign; benign and malignant neoplasms are detected; all tumors are malignant.
- Taking into account the sequence of detection: synchronous primary multiple tumors (detected simultaneously or almost simultaneously), metachronous (diagnosed with an interval of 6 months or more), metachronous-synchronous and synchronous-metachronous.
- Taking into account functional relationships: hormone-dependent, functional-dependent, unsystematic.
- Taking into account the origin from a certain tissue: initially multiple tumors of the same origin and of different origin.
- Taking into account the histological features: the same histological structure, different histological structure.
- Taking into account localization: located in one organ or paired organs; affecting several organs of the same system; localized in organs of different systems.
Diagnostics
The basis for the successful diagnosis of primary multiple neoplasias is a comprehensive approach developed taking into account the peculiarities of the occurrence and course of this group of diseases. One of the most common problems with the detection of primary multiple tumors is the lack of a clear clinical picture characteristic of each neoplasm. Manifestations of neoplasias may overlap with each other, the symptoms of one of the lesions may be weakly pronounced, disguised as a non-tumor disease or mimic the signs of distant metastases.
Thoughtful plans for primary and subsequent examinations, drawn up taking into account the possibility of the development of primary multiple tumors, allow at least partially solving this problem. So, when a solitary neoplasm is localized in the breast area, specialists pay close attention to the condition of the second breast and internal female genitalia, when neoplasia is located in the stomach area – the condition of the large intestine, skin, ovaries, uterus and mammary glands, etc. The examination plan is made individually in each case. Radiological techniques (radiography, CT), ultrasound, MRI and histological studies usually play a decisive role in making a diagnosis.
The probability of developing primary multiple tumors in cancer patients is 6 times higher than the average population. Taking into account this circumstance, all patients with such diseases after treatment should be under medical supervision and undergo regular examinations. This measure allows to detect recurrences of primary neoplasia and diagnose metachronous primary multiple tumors. The risk of developing a second oncological lesion increases at the age of 55-70 years, which should be taken into account when planning a patient examination.
Treatment
Treatment of synchronous neoplasia is carried out simultaneously. Depending on the localization of neoplasms and the patient’s condition, surgical intervention can be carried out at a time or be phased. When planning the sequence of operations for primary multiple tumors, the degree of prevalence of each oncological process is taken into account. In some cases, radical treatment may be carried out for one neoplasm, and symptomatic or palliative treatment for another.
When choosing conservative methods, they focus on the sensitivity of each tumor to radiotherapy and various chemotherapy drugs. The tactics of treatment of metachronous primary multiple tumors corresponds to the tactics of treatment of solitary neoplasms of similar stages and localizations. The prognosis is determined by the type, location, stage and degree of malignancy of primary multiple tumors. The long-term results of treatment of metachronous neoplasia approximately coincide with the results of therapy of single formations. With synchronous processes, the prognosis worsens.