Leaf-shaped tumor of the breast, treatment. How do phyllodes tumors develop in the breast? Leaf-shaped fibroadenoma in elderly women

Leaf-shaped fibroadenoma of the mammary gland or phyllodes tumor is a fibro-epithelial formation and a borderline form between ordinary fibroadenoma and sarcoma, arising from intraductal fibroadenoma. The leaf-shaped tumor got its name because of its specific structure, reminiscent of leaf veins. This fibroadenoma belongs to the group of potentially malignant tumors.

Characteristic

A leaf-shaped tumor is a clearly demarcated compaction with a lobular structure that does not have its own capsule. Fibroadenoma is usually very mobile and does not stick to the skin. In cross-section, the dense lesion contains a viscous mass of mucus and consists of slit-like cavities with small cysts. A large tumor has polyp-like growths in the cystic cavities. This type of tumor may contain one or several nodules. Compared with ordinary fibroadenoma, a leaf-shaped tumor is more different complex structure and large polymorphism of stromal cells.

Leaf-type fibroadenoma can occur in women of any age, but the most common periods are considered to be periods of hormonally active age: 11-20 years, 40-50 years. Quite rarely, such formation is found in men. This neoplasm is prone to rapid development, degeneration into a malignant tumor and relapse. With large leaf-shaped breast fibroadenomas, the skin of the breast becomes thinned, with dilated saphenous veins clearly visible and a bluish tint to the affected area of ​​the breast.

Leaf-shaped tumor is divided into 3 main forms:

• benign;
• malignant;
• borderline or intermediate.

The size of a leaf-shaped breast tumor ranges from 1 to 35 cm, which does not matter, because even the smallest tumor can be malignant. Fibroadenoma foliaceae may be accompanied by chest pain and nipple discharge. Malignant breast tumors can metastasize to skeletal system, liver or lungs.

Causes

It has not yet been possible to determine the exact causes of the occurrence of phyllodes tumor, but usually leaf-shaped fibroadenoma and its appearance are associated with an imbalance in estrogen production and a decrease in progesterone. The following factors are considered to provoke its appearance:

• pregnancy;
• lactation;
• repeated abortions;
• fibrous- cystic mastopathy;
• diabetes;
• obesity;
• tumor thyroid gland;
• ovarian tumors;
• uterine fibroadenoma;
• pathological processes of the liver;
• other processes that cause hormonal imbalance in the body.

Flow of this disease has a staged nature; at the beginning, the process of development of education can occur hidden and without obvious symptoms. A leaf-shaped tumor can remain dormant for a long time, but various factors, including pregnancy, can provoke its growth. Leaf-type breast fibroadenoma can develop slowly, its growth period sometimes reaching up to 10 years.

Diagnostics

To accurately determine the type of tumor and its nature, you need to undergo a series of examinations, including ultrasound, palpation, mammography, Dopplerography, puncture biopsy and cytological examination of the material.

Palpation reveals compaction, delimitation of the tumor, and the number of nodes. Ultrasound of the mammary gland reveals a hypoechoic junction with multiple fluid cavities and crevices, resembling a head of cabbage in structure. Doppler ultrasound reveals the network of various veins and arteries surrounding the fibroadenoma. Mammography determines the shape of fibroadenoma, its structure and intensity of development. Cytological evaluation of the tumor is necessary preoperatively.

Treatment

For leaf-shaped fibroadenoma, radiation and hormone therapy, lymphadenectomy, during which the lymph is removed, is also not performed. A benign leaf-shaped tumor with a diameter of no more than 1 cm does not require urgent treatment; it is enough to be regularly observed and examined using ultrasound and mammography tests. When a benign phyllodes fibroadenoma enlarges or grows rapidly, an operation called “enucleation” is performed - enucleation of the tumor or “quadrantectomy”, removing a quarter of the mammary gland.

Fibroadenoma of a malignant nature with rapid growth and large size requires immediate surgical intervention. This operation is performed by sectoral resection - removal of the cancer along with the surrounding tissue.

Leaf-shaped tumor is also dangerous because it is prone to relapses, the duration of which ranges from a month to 5 years. Benign fibroadenoma breast cancer can degenerate into a borderline or malignant form. In case of repeated relapse, the entire mammary gland is removed. After radical measures, mammoplasty can be performed either using one’s own tissue or with endoprostheses.

Leaf fibroadenoma is insidious disease, the course of which is characterized by unstable and sudden development, which can lead to malignancy of the tumor. At early detection The prognosis for treatment is quite favorable. Therefore, women are recommended to undergo a timely examination by a mammologist and regularly examine their breasts by touch in order to promptly identify and prevent the development of dangerous fibroadenoma of the mammary gland of the leaf-shaped type, as well as to avoid surgical interventions that deform the mammary gland.

Leaf-shaped tumor of the mammary gland is the formation of a fibro-epithelial plan on the mammary gland. It belongs to a number of potentially malignant tumors. The manifestation of a leaf-shaped tumor is the compaction of gland tissue, in some cases reaching large sizes. Sometimes appears with painful sensations, as well as discharge from the nipple. Diagnostics includes such medical aspects as mammography, ultrasound, puncture biopsy and examination of material at the cytological level. Treatment of this disease is exclusively surgical, sometimes including sectoral, radical resection or mastectomy.

Among other things, leaf-shaped disease of the mammary glands in the mammology section can be found with such names as intracanalicular, giant, phyllodes and other fibroadenomas. By the way, like other component manifestations on the mammary gland, this tumor is distinguished by the proliferation of connective tissue as well as epithelial components, with the active advantage of the first. Among all known fibro-epithelial formations on the mammary gland, a disease such as a leaf-shaped tumor occurs in 1.2-2% of cases.

A leaf-shaped tumor that appears on the mammary gland is also a difficult to diagnose formation, prone to active growth, the possibility of relapse, malignant degeneration into sarcoma. The transition of a leaf-shaped tumor to a malignant “level” is possible in 3-5% of three to five percent of cases.

Characteristics of leaf-shaped tumors that appear on the mammary gland

The histological international classifier inclines the leaf-shaped tumor into the ranks of fibro-epithelial formations, identifying three probable forms - benign, malignant, and also the so-called borderline, which is an intermediate form.

The macroscopic appearance of a leaf-shaped tumor depends on the size of the formation. For example, a five-centimeter tumor in diameter is shown as a serious formation separated from other tissues, pinkish or white-grayish in color, with a lobulated or coarse-grained structure. At the junction, you can notice small cysts and slit-like cavities, into which a viscous mucus-like mass enters. The macrostructure of leaf-shaped tumors on the mammary gland, which exceeds the five-centimeter mark, is shown in the form of cystic slits and cavities, which are filled with polyp-like growths in the area of ​​the cystic cavities, as well as a gelatin-like secretion.

If you examine a leaf-shaped tumor of the mammary gland microscopically, you will notice the predominance of the stromal (connective tissue) element. The difference between a leaf-shaped tumor and a fibroma appears in the form of a more pronounced stroma with serious manifestations of proliferation and polymorphism of stromal cells.

Also, a leaf-shaped tumor can appear as single or multiple nodes, the location of which is concentrated in one or all mammary glands. Phylloid tumors are characterized by sudden, dynamic growth. The sizes of leaf-shaped fibroadenoma can be very different - from small nodules to tumors of twenty or more centimeters in diameter.

Causes of a leaf-shaped tumor on the mammary gland

The etiological component of the leaf-shaped tumor is not completely known. Its developing process is associated with a breakdown in the hormonal balance, primarily with hyperestrogenism, as well as an insufficient amount of progesterone. Based on this, the phases of detection of phyllodes fibroadenomas fall during periods of hormonal transition activity in women: from eleven to twenty years, and much more often - from forty to fifty. It is very rare, but you can still find leaf-shaped tumors on the male mammary glands.

The provoking factors for the appearance of leaf-shaped tumors on the mammary glands are the following: abortion, pregnancy, cystic fibrous mastopathy, lactation, extragenital endocrinopathies, as well as metabolic disorders such as diabetes mellitus, tumors of the pituitary gland and adrenal glands, thyroid gland, obesity, liver disease and others.

Symptoms of the formation of a leaf-shaped tumor on the mammary glands

Leaf-shaped tumor, in the vast majority of cases, occurs in two phases. As a rule, at the end of a long period of slow development, which can sometimes drag on for decades, the process enters a phase of unexpected dynamic growth. On average, the size of phyllodes fibroadenomas reaches five to nine centimeters, although there have been cases of tumors reaching a diameter of forty-five centimeters and a weight of about seven kilograms. It is noteworthy that the prognosis of a leaf-shaped tumor does not depend on its size - even a small formation risks becoming malignant, just as a huge fibroadenoma can act as a benign one.

As a rule, a leaf-shaped mammary tumor is discovered by the patient herself or a mammologist after palpation; it looks like a dense node. When the tumor reaches enormous sizes, the skin over the female breast becomes thinner, acquiring the corresponding color, under which you can even see expanded saphenous veins. In addition, pain may begin in the mammary gland, ulcers may appear on the skin, and the affected gland may be released from the nipple.

The location of a leaf-shaped tumor is mainly noticed at the top or center of the breast, and if the tumor is large, then it can completely occupy the breast or most of it.

A leaf-shaped tumor of a malignant nature mainly affects the liver, bones and lungs. Lymph nodes, in turn, are not affected.

Diagnosis of a leaf-shaped tumor on the mammary gland

During palpation, a leaf-shaped tumor on the mammary gland is identified as a compaction, which is clearly demarcated from nearby tissues. The seal has a lobed structure, which includes several interconnected nodes.

When performing an ultrasound of the female mammary glands, specialists identify a hypoechoic formation, which in its cross-section resembles something like a head of cabbage. It has a heterogeneous structure, as well as many anechoic (fluid) cracks and cavities. Doppler ultrasound inside the formation of nodes on the mammary gland helps to identify a multiple chain of diverse arteries and veins. Mammography, in turn, helps to identify a tumor conglomerate of oval (regular) or round (irregular) shape with a lobular structure and clear outlines. A remarkable fact here is that the tumor shadow is a homogeneous and rather intense body.

The importance of preoperative differentiation in relation to a benign leaf-shaped tumor of the female breast, as well as sarcoma, necessitates a cytological assessment of the formation. This goal explains the conduct of a puncture biopsy of the tumor from its various areas, followed by a cytological examination of the biopsy.

Treatment of leaf-shaped breast tumor

Due to the rapid progress, many variants of the course, as well as the increased potential for transition to a malignant form, in relation to a leaf-shaped tumor, only surgical tactics are prescribed.

In case of the appearance of benign, as well as intermediate tumors of the leaf-shaped type, a quadrantectomy or sectoral resection female mammary glands. Radical resection of the mammary glands, subcutaneous or radical mastectomy will be useful if the tumor is huge or malignant. At the same time, lymphadenectomy is performed extremely rarely. In the event of radical interventions, the patient undergoes reconstructive mammoplasty using personal tissues or endoprostheses.

Radiation and hormonal therapy are not used when a leaf-shaped tumor is detected.

Prognosis for leaf-shaped tumor

A distinctive feature of leaf-shaped formations on the mammary glands is their intense tendency to relapse: as observations show, phyllodes fibroadenomas of a benign nature reappear in only 8.1% of cases, while more dangerous, borderline and malignant ones can occur in 25 and 20% percent of cases, respectively.

In the vast majority of cases, the occurrence of relapses is noticed within a period of several months to approximately two to four years. Besides, in given time there is a possibility of the tumor transitioning from benign to sarcomatous or intermediate.

By increasing the intensity of the intervention (that is, the use of mastectomy), the risk of recurrence of a leaf-shaped formation on the mammary gland is minimized.

In one case or another, with the prevention and treatment of the described illness, the main thing is not to hesitate under any circumstances and, at the first suspicion, immediately contact a specialist.

Malignant and benign neoplasms are the most common type of mammary gland pathology. Special place Among them is a leaf-shaped tumor. The disease is rare, is under study, and is difficult to diagnose. It is registered in 0.3-1% of all cases of mammary gland pathologies.

Phylloid tumor of the mammary gland is a mixed fibroepithelial neoplasm. It is distinguished by the diversity of its structure and clinical manifestations: it consists of two components - epithelial and mesenchymal (stromal, connective tissue). Currently according to histological structure There are three variants of pathology:

1. Benign.
2. Intermediate.
3. Malignant.

They differ in the ratio of the two tissue components, contours, and the variety of changes in the structure of cell nuclei. According to international studies, the frequency of the malignant form occurs in 2-40% of cases. When studying microscopic specimens, in 25% of cases there is a discrepancy in diagnoses. The information content of a cytological examination reaches one third of all examinations.

The malignant potential of a leaf-shaped tumor belongs to the connective tissue component, which can degenerate in a small area, while its main area is benign. This feature often leads to erroneous histological conclusions - in cases of breast biopsy outside the localization of malignant cells. There is conflicting data on clinical manifestations, growth characteristics, recurrence, and the relationship of the neoplasm with the mammary glands.

Primary diagnosis is difficult due to the lack of pathognomonic (inherent only to this pathology) symptoms and signs during instrumental examination methods. In small tumors, it is difficult to determine the malignancy of the process and to distinguish a leaf-shaped tumor from another pathology of the mammary gland. These difficulties explain the heterogeneity of views on the disease - the nature of its occurrence, the principles of treatment.

Causes of development, predisposing factors

Currently, debate continues about the mechanism of development of leaf-shaped tumors - a number of scientists believe possible occurrence diseases from a previous fibroadenoma, some authors consider its appearance as an independent new formation from the mammary gland parenchyma. Discussions are also generated by factors influencing the occurrence of this pathology:

• increased estrogen content;
• or lack thereof;
• hormonal changes during pregnancy and lactation;
• diseases of the female genital organs;
• diabetes;
• diseases of the thyroid gland, liver;
• traumatic injuries;
• overweight;
• diffuse cystic mastopathy, breast fibroadenoma.

Scientists suggest that disruption of the production of hormones (somatotropic, estrogen, cortisol) may have Negative influence on the connective tissue of the mammary gland. It is theoretically possible, with an increase in the level of estrogen and glucocorticoid hormones, the occurrence of fibroadenoma. If hyperproduction is added to these processes growth hormone– connective tissue grows and cells transform.

The disease occurs at any age from the onset of puberty to old age, occurs in men and women, more often in the reproductive period. It can transform into cancer - the epithelial component into carcinomas, the connective tissue component into sarcomas, and with the transformation of two components, carcinosarcomas develop. This ability to malignize is distinctive feature phyllodes tumors. Metastasis occurs through blood vessels to the bones, lungs, and liver.

Diagnostics

The presence of a heterogeneous structure of the formation, errors in the examination of biopsy material - microslides, cytology, the lack of uniform standards for interpreting research results lead to the fact that correct diagnosis is before surgical intervention carried out in a quarter of cases. This result is considered unsatisfactory. In the process of finding out the truth, an oncologist, a histologist, and a specialist must be involved radiology diagnostics.

Complaints

The main reason for a patient to see a doctor is the presence of palpable single or multiple lumps in the chest, most often in the upper outer and central parts on one side. They may be accompanied by pain and discharge from the nipple. Some women do not complain; the disease is detected during preventive examinations.

What does the doctor see?

The examination picture is not specific; upon palpation, a formation with clear contours, a lumpy or elastic consistency, measuring from one to thirty-five centimeters is determined in the tissue of the organ. The skin over it is most often unchanged; fixation, a symptom of wrinkling, is extremely rarely detected. In the vast majority, thinning, cyanosis, dilatation of subcutaneous vessels, and ulceration are visible. Swelling of the nipple and areola and, in some cases, smoothness are observed.

In 17% of patients, enlarged lymph nodes are detected on the affected side. It has been noted that small tumors (up to 5 cm) can be present in 95% of cases. There is an algorithm developed by oncologists for examining women with suspected leaf-shaped breast tumors.

Existing research methods do not allow one to reliably differentiate different histological variants of this pathology. Thus, accurate diagnosis is possible with histological examination microslide.

Morphology

When examining a small removed tumor, a solid tissue component with small liquid inclusions is determined, with sticky mucus. In larger formations there are large cysts with a bloody or gelatinous mass, polyp-like growths in the form of cauliflower. In large neoplasms, pathological nodes of dense consistency, similar to cartilage tissue, with many slit-like cavities are determined. Microscopy reveals the ducts that line the epithelial and myoepithelial cells and the stroma growing into them, forming typical leaf-like structures.

Histological signs of leaf-shaped tumors are the predominance of connective tissue (spindle-shaped cells such as fibroblasts) over epithelial tissue in combination with multicellularity. The malignant form of pathology is distinguished from sarcoma by the presence of epithelial cells in its structure. In modern oncology centers it is performed after a puncture biopsy. cytological analysis drugs (DNA histograms). For this purpose, laser analyzers and modern computer programs are used to analyze the distribution of pathological cells across the phases of the cycle and detail their number.

This method made it possible to identify differences in the structure individual species leaf-shaped tumor. Most complex diagnostics requires a border form containing cells on different stages malignancy. In the presence of a malignant process, the nuclei have an elongated shape, the cells lie separately.

Radiography

Despite the fact that to date no reliable criteria have been established in the radiological diagnosis of a leaf-shaped tumor that would allow distinguishing all variants from other diseases of the mammary glands, it is indicated if there is a suspicion of any neoplasm of this organ. The study is carried out in direct, oblique and lateral projections using a special X-ray machine - a mammograph in the middle menstrual cycle.

When the lesion size is up to 5 centimeters, in 76% of cases it is not possible to distinguish a benign phyllodes tumor from a fibroadenoma - both give a homogeneous darkening with clear, even contours. Formations over five centimeters in diameter, having uneven contours, a heterogeneous structure with cystic inclusions can be suspected as a leaf-shaped tumor of the mammary gland. The study is contraindicated for pregnant and lactating women.

Ultrasound

The method has a number of advantages for examining the mammary glands in young women under 35 years of age. Sonography is carried out using linear sensors with a frequency of 7.5-10 MHz. The degree of information content for confirming the diagnosis of phyllodes tumor according to the literature is ambiguous. A number of scientists note the ability to recognize benign and malignant formations. According to other sources, only differences are determined between cystic and solid structures in young women with a glandular structure of the glands.

The following signs are identified that speak in favor of the disease:

• a picture of a solid hypoechoic or isoechoic formation;
• heterogeneity of the structure with the presence of round and slit-shaped cavities;
• good demarcation from surrounding tissues;
• the presence of a hyperechoic rim, lateral acoustic shadow and dorsal enhancement in the absence of a central one;
• the structure of the formation resembles a head of cabbage when cut.

When pulsed Dopplerography with color mapping is observed, there is a varied proliferation of blood vessels, a decrease in blood flow velocity, and a low peak velocity. However, a small number of observations does not allow these signs to be considered reliable for this type of formation. Ultrasound diagnosis of leaf-shaped breast tumors is varied; there are new modern modes of operation of the devices.

Ultrasound with contrast

An additional examination method is contrast-enhanced ultrasound - when a contrast agent is injected, uneven chaotic contrast enhancement followed by washing. At the same time, the nature of the kinetic curve of this process and the nature of the vascular picture are assessed. The malignant process corresponds to the third type of kinetic curve and the spiral nature of the vascular pattern.

Sonoelastography

With the aim of differential diagnosis benign and malignant forms, they use a modern diagnostic method - sonoelastography (SEG). Using color mapping in real time, the density and elasticity of fabrics is determined - different fabrics have their own level (stiffness coefficient and elastotype). The rigidity of formations is assessed based on an analysis of their qualitative and quantitative characteristics. The diagnostic accuracy reaches 70% for this pathology. The study is carried out after identifying the pathological focus, using ultrasound machines that have a special operating mode.

Scintimammography

This method of radiation diagnostics using a gamma camera is based on the use of labeled radioisotopes capable of selective accumulation in organs and tissues. The study is used in large oncology centers for the differential diagnosis of benign and malignant processes in the mammary glands according to the nature and level of accumulation of the radioisotope in the node. Phylloid tumor of the breast can be diagnosed using MRI.

Magnetic resonance imaging

The technique is an additional clarifying examination in the presence of nodular formations of the mammary glands, it is non-invasive, safe, and informative. The study is performed in three planes using special magnetic coils; a gadolinium-based drug is used for contrast.

Indications for MR mammography with dynamic contrast:

• suspected in young women with a dense organ structure;
• difficulties in diagnosing by other methods;
• edema, fibrosis, post-mortem condition surgical treatment mammary gland;
• localization of pathological changes in the retromammary space;
• the presence of enlarged peripheral lymph nodes.

MR mammography is recommended to be done between 6-14 days of the menstrual cycle to exclude artifacts, scanning is carried out before and after the administration of contrast. The technique makes it possible to identify and accurately localize X-ray negative, multinodular and diffuse forms of neoplasms less than 1 cm in diameter based on the nature of contrast accumulation. On MRI, a leaf-shaped breast tumor can have either a homogeneous or heterogeneous structure. It may be a lobular conglomerate separated by septa with high signal intensity. Slit-like cystic cavities are often identified, based on visualization of which it is possible to distinguish different variants of the disease.

For a benign option

Characterized by smooth edges of the cavities and a homogeneous hypointense signal, the absence of disturbances in the structure of the surrounding tissues, and the predominance of the longitudinal size of the formation. When contrasting, the substance accumulates minimally and homogeneously, there is no deformation of the vascular network of the gland.

Malignant variant

When visualized, it suggests cystic cavities with irregular edges, heterogeneous signal, and a predominance of transverse size. When contrasting, foci of decay and hemorrhage, a heterogeneous MR structure, intense accumulation of contrast, and asymmetry of the vascular network are determined.

Oncologists note that the categories of the Breast Imaging Interpretation and Documentation System (BI-RADS), assessed using MRI most reliably, compared with other methods of radiodiagnosis, coincide with the histological variant of the tumor. The diagnostic value of the method when using BI-RADS categories is 95.8%.

Tumor markers

Genetic studies of phyllodes tumors are rarely performed. From published data it follows that carriers of the BRCA1/2 gene mutation are more likely to develop a malignant leaf-shaped tumor; the TP53 gene determines the progression of the disease. Modern research detect changes in the genotype of cell nuclei. The prognostic significance of the series is currently being studied.

Therapy methods

A feature of phyllodes tumors is an increased tendency to recur with malignant degeneration cells for 2-5 years. In a quarter percent of cases, borderline and malignant neoplasms recur. Relapse rate benign tumors three times less. A number of scientists believe that the reason for this is the insufficient volume of surgical intervention, because the leading method of treating this pathology is surgical.

Different oncology schools have their own approach to addressing issues of disease therapy. Treatment of leaf-shaped tumors of the mammary glands does not have a uniform approach today.

In a benign form, some authors consider it sufficient to perform. For malignant and intermediate - amputation or. Other oncologists insist on mastectomy for all forms of the disease, considering it justified due to the frequency of relapses.

Removal of peripheral lymph nodes is performed in the presence of metastases, but there is no data confirming the effectiveness of the manipulation. Russian oncologists have described cases of successful surgical treatment leaf-shaped tumor of the mammary gland of large size during pregnancy with subsequent birth healthy child, no relapse of the disease for 7 years.

The effectiveness of radiotherapy in the treatment of this pathology has not been sufficiently studied. Available observations of the use of ionizing radiation in metastases and relapses indicate the absence of a significant effect. Leaf-shaped tumors are insensitive to chemotherapy, recommendations for systemic application There are no chemotherapy drugs.

Currently, studies are being conducted for individual therapy of patients, which consists of influencing target genes; a case of treatment with Sunitinib has been reported with a good result.

Forecast

Currently, a search is underway for morphological, clinical, genetic, molecular factors that influence the outcome of the disease and the development of relapses that can predict the sensitivity of a leaf-shaped breast tumor to radiation therapy, systemic treatment. Based on a few observations, it was found that the five-year survival rate for malignant forms is 58.5%, relapses occur in 28% of cases.

The group of fibroepithelial tumors of the mammary gland includes two-component tumors with proliferation of connective tissue and epithelial components. Fibroadenomas - quite common tumor mammary gland, and leaf-shaped tumors are relatively rare in oncological practice and do not exceed 2% of all fibroadenomas.

Leaf-shaped tumor (leaf-shaped fibroadenoma, giant myxomatous fibroadenoma, intracanalicular fibroadenoma with cellular stroma, phyllodes fibroadenoma, etc.) is similar to fibroadenoma, but is characterized by a predominance of the connective tissue component. Leaf-shaped tumors are difficult to diagnose formations with an unpredictable course, a tendency to recur and a high probability of malignancy.

In the WHO International Histological Classification (1995), in the section of fibroepithelial neoplasms, a group of leaf-shaped tumors (9020/0) is identified with 3 possible forms - benign, borderline and malignant.

Leaf-shaped tumor characterized by the potential for transformation into breast sarcoma due to malignant changes in the stroma. In addition, the presence of an epithelial component does not exclude the development of carcinoma. A mixed malignant tumor or carcinosarcoma of the breast may also be the product of these changes in the 2 components of a leaf-shaped tumor. Features of morphogenesis, proliferation of the stromal component, and the nature of epithelial-stromal relationships dictate the need for parallel study of leaf-shaped tumors and breast sarcomas. Breast sarcomas are divided into 2 groups according to pathogenesis: tumors arising from leaf-shaped tumors and tumors from the breast stroma. In stromal sarcomas, no evidence of a previous leaf-shaped tumor can be detected.

According to the variants of histological forms, sarcomas from a leaf-shaped tumor do not differ significantly from stromal sarcomas of the mammary gland, however, the latter are characterized by less favorable clinical course and, as a rule, after treatment lead to death within 3 years. The source of development of stromal sarcomas is the pluripotent mesenchymal rudiment, which has numerous directions of differentiation. It is assumed that in conditions of disruption of the regenerative process (possibly after injury), mesenchymal cells can be formed that lose the ability to undergo normal differentiation and can become a source of malignant neoplasm. Until now, leaf-shaped tumors and sarcomas of the mammary gland remain difficult to identify and are characterized by problematic diagnosis and treatment. In the literature, the question of the role of the cytological method in recognizing rare fibroepithelial tumors is not sufficiently covered.

This study allows us to judge the process before the start of treatment, when the most reliable information is needed to confirm the clinical diagnosis. As a result, accurate diagnosis allows you to correctly choose the treatment method, the optimal amount of surgical intervention and determine the outcome of the disease. Based on the analysis of our own data, we assessed the capabilities of the cytological method for diagnosing leaf-shaped tumors and breast sarcomas. The work is based on the results of clinical and morphological data concerning 120 patients examined with rare fibroepithelial tumors of the mammary gland. Benign leaf-shaped tumors (Fig. 1) were identified in 74 (61.7%) patients, borderline forms of leaf-shaped tumor - in 12 (10.0%). Sarcoma, carcinosarcoma and malignant leaf-shaped tumor were found in 34 (28.3%) patients, which accounted for 0.56% of all malignant breast tumors.

Rice. 1. Benign form of leaf-shaped tumor. Uv. 100

The puncture was performed by oncologists at the outpatient clinic stage of examining patients (standard technique). Disposable instruments were used: a syringe with a volume of 10-20 cm3, needles 60 mm long with an outer diameter of more than 1 mm. For small formations, a single puncture was used; for tumors with a diameter of more than 3 cm, and especially in cases with heterogeneous tumor consistency (alternating dense areas and softening areas), 2-3 punctures were performed from different areas. The heterogeneity of the histological structure of rare fibroepithelial tumors necessitated a cytological study of several areas in the area of ​​detected changes (minimum 2); material from each area was applied to a separate glass. The preparations were stained using the Pappenheim method and studied in light microscope. For all operated patients with an established cytological diagnosis, the results obtained were compared with subsequent histological examination. The information content of the cytological method was assessed using standardized indicators. Cytological preparations were divided into groups: benign, borderline, and malignant lesions.

The search for objective differential diagnostic criteria for rare fibroepithelial breast tumors requires the use of modern technical approaches. We analyzed the DNA content in tumor cells using flow cytofluorometry. To do this, thick (50 µm) sections were cut from the material of paraffin blocks on a microtome using a special technology to obtain a cell suspension according to the method of R. Camplejonh et al. (1985) and D. Hedley (1983,1989) in our modification. For this purpose, tumor areas were selected in which cells accounted for more than 50% of the area of ​​the histological section. The cellular composition of the suspension and its homogeneity were controlled under a microscope using the Cytospin method (Shandon Co., UK). The concentration of cells in the suspension was adjusted to 12 106 in 1 ml. Then 0.4 ml of a cold (4°C) solution of propidium iodide (Sigma, USA) was added to 0.2 ml of the suspension and the resulting mixture was shaken several times. The stained cell suspension was analyzed on an EPICS-XL laser flow analyzer (Beckman-Counter, USA). At least 50 thousand cells were examined in each sample. In the resulting DNA histogram, the percentage of cell nuclei with different DNA contents was calculated in relation to the total number of cells studied. The obtained data were analyzed using modern computer programs: System IITM (Version 3.0, Beckman-Coulter, USA), which allows analyzing the ploidy and distribution of tumor cells by phase of the cell cycle, and the latest program also details the number of cells in the S- and G2+M-phases. The obtained data were analyzed in comparison with the available cytological characteristics.

The most common clinical manifestation of all rare fibroepithelial tumors of the mammary glands is the presence of a tumor formation with fairly clear contours and a bumpy surface, usually painless, which does not allow distinguishing sarcoma from benign and borderline forms of a leaf-shaped tumor. Among the patients we examined, who were aged from 12 to 75 years, the majority of patients with a benign form of a leaf-shaped tumor belonged to the age group from 30 to 49 years, the borderline form of the tumor was in women from 40 to 54 years, and malignant (sarcomas and carcinosarcoma ) - in the age group from 40 to 75 years. The age limit for a benign form of a leaf-shaped tumor is on average 20 years less than for malignant fibroepithelial tumors.

The most common location of leaf-shaped tumor and sarcoma is the upper and central quadrants of the breast (63.2%). If the tumor was large, it occupied the entire or most glands (36.4%). Rare fibroepithelial tumors ranged in diameter from 1 to 30 cm. In most cases, one tumor formation was found, but in some cases multiple (up to 6) formations were noted in the mammary gland. Lymph nodes were not palpable in most patients, and no metastases to the lymph nodes were detected. No nipple discharge was noted. A feature of phyllodes tumors is an increased tendency to recur. The recurrence rate of the benign form of the leaf-shaped tumor, according to our data, was 8.1%, the borderline form - 25%, and the malignant form - 20%. Relapses were noted within 2 months. up to 2.5 years, while recurrent tumors were similar in structure to the primary one only in 28.6% of cases; in the remaining cases, sarcomatous transformation of cells was noted.

The results of a comparison of cytological and histological data in patients in this group showed that the cytological picture in most cases reflects the features of the histological structure of the tumors. This determines the validity of cytological verification of rare fibro-epithelial breast tumors. When studying and evaluating cytological criteria in a preparation, one should take into account the features of the cytological method, due to the fact that when preparing a smear, the spatial relationship of cells that exists in the original tissue is disrupted.

The most significant cytological feature characteristic of leaf-shaped tumors is the presence in the preparations of areas of oxyphilic fine-grained masses with fibroblast-like cells embedded in them. The epithelial component of the tumor is represented by proliferating cubic epithelium lining the tumor clefts and connective tissue outgrowths.

Based on a cytological examination of patients, it was proposed to distinguish 4 variants of the cytological picture for a benign form of a leaf-shaped tumor:

1. with the obligatory presence of connective tissue and epithelial cell elements;
2. with a predominance of the epithelial component and a poorly represented connective tissue component;
3. with a predominance of cellular elements resembling the cellular composition of the contents of the cystic cavity;
4. with scant stromal and scant epithelial components.

It should be noted that an accurate cytological diagnosis of a benign form of a leaf-shaped tumor is possible only with option 1.

It is necessary to differentiate benign leaf-shaped tumors with an insufficiently expressed stromal component with:

• intra- and pericanalicular fibroadenomas;
• highly differentiated adenogenic cancer;
• proliferative form of fibroadenomatosis.

The borderline form of a leaf-shaped tumor is the most difficult for cytological diagnosis. The structure of such tumors is a reflection of a certain stage in the process of gradual malignancy. Borderline tumors differ from benign tumors in several features inherent to the entire tumor as a whole: proliferation of the stromal component; the presence of extensive structures of fibroblast-like cells; an increase in the number of mitoses; signs of nuclear atypia.

In the borderline form of a leaf-shaped tumor, the detection of stromal cells with nuclear polymorphism is representative. In contrast to the benign form of a leaf-shaped tumor, fibroblast-like cells form extensive groups and layers, immured in oxyphilic masses, along with a large number of separately located stromal elements. Cellular stroma with pronounced nuclear polymorphism is alarming regarding the malignant nature of the tumor, but convincing signs of sarcoma are not observed in cytological pictures (Fig. 2).

Rice. 2. Borderline form of leaf-shaped tumor. Uv. 400

Malignant leaf-shaped tumors are often characterized by a long history (one of the women was observed for 17 years). The ratio of benign leaf-shaped tumors to borderline and malignant forms was 66.2 / 15.0 / 18.8.

The term " malignant leaf-shaped tumor "It is problematic to use in cytological diagnosis, since it is possible to differentiate a malignant leaf-shaped tumor from other mammary gland sarcomas only when the epithelial component is identified. A definite cytological diagnosis of a malignant leaf-shaped tumor is impossible in many cases, but the presence of certain cytological features allows a presumptive diagnosis to be made. A cytological diagnosis of a malignant leaf-shaped tumor may look like this: sarcoma, probably a malignant leaf-shaped tumor. Cytological preparations of a malignant leaf-shaped tumor reveal large areas of oxyphilic masses in which numerous tumor cells are immured. Oxyphilic masses form strands in the form of bright crimson thread-like substances (Fig. 3).

Rice. 3. Malignant form of leaf-shaped tumor. Uv. 1000

Differential diagnosis of malignant leaf-shaped tumor is difficult. Abundant oxyphilic masses in epithelial tumors of the mammary glands are rare; they can be represented by stromal amyloidosis or cellular detritus. In the tumor cells of a malignant leaf-shaped tumor, the nuclei are mainly elongated; among the abundant oxyphilic masses, separately lying tumor cells are most often observed, solidly located throughout the oxyphilic masses, as if immured in them, not forming glandular-like complexes. According to the histological structure of sarcomas arising from a leaf-shaped tumor, they were represented by a malignant leaf-shaped tumor in 7 (46.7%) cases, fibrosarcoma - in 3 (20.0%) patients, as well as 2 (13.3%) cases of lipo-and leiomyosarcoma and 1(6.7%) myxosarcoma. Cytograms of fibro-, lipo-, leiomyo- and myxosarcomas corresponded to cellular composition identical soft tissue tumors. Retrospective comparison of cytological and histological data with clinical data allowed us to classify these cases as malignant forms of leaf-shaped tumor. In all of these observations, histological examination of the tumor revealed areas characteristic of a leaf-shaped tumor, or a leaf-shaped tumor was previously present in the surgical material.

Breast stromal sarcomas constitute group 2 (35.3%) and have the most malignant clinical course. This includes tumors that do not have tissue analogues in this organ. With stromal sarcoma, the medical history is short: from 2 weeks to 2 months. In 4 (33.3%) observations, the histological interpretation of sarcoma corresponded to malignant fibrous histiocytoma, in 2 (16.7%) - histologically, in addition, there were 2 (16.7%) observations of “malignant mesenchymoma”, fibro- and osteosarcoma , as well as 1 (8.3%) each of angio- and neurogenic sarcoma. The cytological picture in malignant fibrous histiocytoma was very diverse (Fig. 4). One of its variants is characterized by 2 types of cells with signs of fibroblasts and histiocytes; in the other, multinucleated cells with centrally located hyperchromic nuclei with abundant oxyphilic, granular cytoplasm are found. In addition to them, fibroblast-like cells with mitotic figures were detected.

Rice. 4. Malignant fibrous histiocytoma. Uv. 1000

In fibrosarcoma, the cytological picture was characterized by fibroblastic tumor cells. The signs of malignancy are quite convincing. Cytograms of breast fibrosarcoma were identical to those of soft tissue fibrosarcoma. In angiosarcoma, the background of the drug consists of erythrocytes and varying numbers of hemosiderophages. Branching tissue patches of small and medium-sized cells of irregular and oval shape are visible. Oxyphilic masses appear in the form of pale pink areas. As a rule, in preparations there is a different number of capillaries, which are hollow tubes lined with endothelium. Microcapillaries are surrounded by cells tightly adjacent to their walls. Neurogenic sarcoma in cytological preparations is characterized by cells immured in oxyphilic masses with bizarre long processes of the cytoplasm. There are giant “simplasts”. Most often, pronounced polymorphism and atypia are observed in cells located isolated from each other (Fig. 5).

Rice. 5. Neurogenic tumor. Uv. 1000

Carcinosarcoma of the breast constitutes the 3rd group of sarcomas. Carcinosarcoma is a malignant neoplasm represented by a combination of elements of cancer and sarcoma within one tumor site. The histogenesis of carcinosarcoma remains unclear for many years. Some authors even questioned the existence of such a nosological form, believing that the mesenchymal component undergoes peculiar changes in the epithelial cells of the tumor, which makes it similar to sarcoma. We observed 3 women with carcinosarcoma. In 2 patients, a sarcomatous component was identified against the background of cancer with squamous cell differentiation. In the 3rd patient, an atypical chondromatous component was noted against the background of cancer. All these cases caused difficulties in cytological diagnosis. In carcinosarcoma, the presence of tumor elements of an epithelial and stromal nature is noted within one area of ​​the viewed cytological specimen (Fig. 6).

Rice. 6. Carcinosarcoma. Uv. 400

The cytological picture of carcinosarcoma differs from that characteristic of breast cancer, as well as malignant leaf-shaped tumor and stromal sarcoma. A study of the DNA content of cells using flow cytofluorometry showed that in the case of a benign form of a leaf-shaped tumor, the samples were diploid. In the borderline form, high diagnostic value this method, since the tumors were both diploid and aneuploid. In one observation, with DNA flow cytofluorometry, the tumor had a high proliferation index (PI = 48.0%) and a significant number of dividing cells (in the G2+M phase - 19.8%), which is close to the indicators of sarcomas; This was later confirmed when the tumor relapsed after 6 months.

DNA flow cytofluorometry allows you to accurately determine the variant form of a leaf-shaped tumor if determining the malignancy of the process at the light-optical level is difficult. In the diagnosis of malignant fibroepithelial tumors of the mammary gland, the use of flow cytofluorometry was confirmed in all cases; all tumors were aneuploid. Repeated cytological studies did not prove the malignant nature of the tumor with a myxoid component. A cytofluorometric study showed that the DNA index was very high in this case - it corresponded to three times the amount of DNA (3.3), as did the indicator of the number of dividing cells (in the S-, G2 + M-phases it was equal to 43.1%). This study convincingly confirms the malignant nature of the tumor, the cytological diagnosis of which presented significant difficulties. DNA flow cytofluorometry has established that analysis of cell ploidy and their distribution across phases of the cell cycle and proliferation index indicates a steady increase in indicators in the S- and G2+M-phases, as well as the proliferation index in the range from benign to malignant leaf-shaped tumors, stromal sarcomas and carcinosarcomas.

Thus, cytological diagnosis of a leaf-shaped tumor and sarcoma of the mammary gland is possible in the 1st variant of the benign form of a leaf-shaped tumor, as well as in determining the non-epithelial (sarcomatous) nature of the tumor in most cases of malignant forms of leaf-shaped tumors and stromal sarcomas. In other forms of benign, as well as borderline leaf-shaped tumors and some malignant forms, it is necessary to use DNA flow cytofluorometry, which more accurately determines the nature of the tumor, which facilitates the correct choice of treatment method.

Authors: O.G. Grigoruk, V.N. Bogatyrev, A.F. Lazarev, V.K. Sokolova, T.S. Frolova, L.M. Bazulina, Altai branch of the State Institution RORC named after. N.N. Blokhin RAMS, Altai Regional Oncology Center, State Institution Russian Cancer Research Center named after. N.N.Blokhin RAMS

Material taken from the magazine “Mammology”, No. 1, 2005