Mediterranean lymphoma of the small intestine: causes, symptoms, diagnosis, treatment

In cases of pronounced dysplasia of lymphoid tissue and malignant lymphomas of plasmacytic differentiation, monoclonal gammopathies are often observed. In this case, the nature of the gammopathies, as a rule, corresponds to the plasma cell secretion of the field in which the lymphoma develops.

Among paraproteinemic hemoblastoses that selectively affect the small intestine, the most common is Seligmann lymphoma, described by him and co-authors in 1968. The names of this disease found in the literature characterize its heterogeneous symptoms: "Seligmann lymphoma", "intestinal form of heavy a-chain disease", "primary lymphoma of the upper small intestine", "Middle Eastern lymphoma", "Mediterranean lymphoma"; according to the WHO nomenclature - "immunoproliferative disease of the small intestine".

Despite the detailed description of cases with a unique clinical and morphological picture, there are no established views on the etiology and pathogenesis of this lymphoma in the literature. Existing hypotheses are based on the possible role of long-term local antigenic stimulation of the small intestine by microorganisms in areas with a high incidence of intestinal infections, as well as on the genetic predisposition of patients, the impact of an oncogenic virus similar in structure to the gene that controls the synthesis of IgA.

This disease occurs mainly in the 2nd and 3rd decades of life, in men - 1.7 times more often than in women.

The pathology is based on primary disorganization in the B-cell lymphocytopoiesis system with characteristic excessive infiltration of the small intestinal mucosa (less often organs where IgA is also synthesized - nasopharynx, bronchi) with cells in which pathological immunoglobulin is determined. Disruption of protein synthesis is expressed in the complete absence of light a- and beta chains of immunoglobulin in the structure of the molecule and the formation of defective heavy a-chains lacking the Fd fragment. Similar changes are also noted in regional lymph nodes. Only 10-25% of the described lymphomas occur with the appearance of a monoclonal IgA component in the blood. This feature allows us to consider this disease as one of three immunochemical variants of heavy chain disease: a-chains (Seligmann), much less common diseases of y-chains (Franklin) and ft-chains (Forte).

At the first stage, symptoms of impaired absorption predominate. Patients complain of loose stools 10-15 times a day, abdominal pain, nausea, vomiting, these symptoms have been noted for several months before seeking medical attention. The skin is pale, slightly flaky, acrocyanosis and severe exhaustion are present. The body weight deficit is 13-27 kg. Cervical, axillary and inguinal lymph nodes are slightly enlarged in some cases. The liver is not enlarged. In isolated observations, the spleen is involved in the process with its slight enlargement. Palpation reveals pain in all parts of the abdomen, especially around the navel. The abdomen is bloated, there is a "doughy" feeling under the arm. The cecum is swollen with gases, rumbling and splashing noises are heard. The stool is liquid, dark green, up to 2500 g per day. In the peripheral blood - moderate anemia, thrombocytopenia up to 9x10 ¹¹ /l, the number of leukocytes varies (5.6-23.0x10 ¹¹ /l) depending on the accompanying inflammation. ESR is accelerated to 25-54 mm / h. The amount of total protein is from 24.5 to 59.6 g / l; albumins - 40-45%; globulins: a1 - 3-4.5%, a2 - 12.3-22%, beta - 15-16.7%, y - 15-22.2%; blood potassium - 2.5-3.7; sodium - 120-126 mmol / l. In an immunological study of peripheral blood lymphocytes - a moderate decrease in the number of T-cells and an increase in B-lymphocytes.

During X-ray examination, against the background of expanded folds of the mucous membrane of the jejunum, scattered multiple unclear, in places merging round and oval filling defects with a diameter of 0.5-0.8 cm are visible, creating a nodular relief. In places, the intestine may be spasmodically contracted, enlarged regional lymph nodes may form small depressions in the intestinal wall.

During endoscopic examination, the mucous membrane of the duodenum and initial sections of the jejunum is loose and red-gray.

When determining immunoglobulins by the radial immunodiffusion method, a decrease in IgG and IgM and a significant increase in IgA up to 4400 x 10 ³ IU/l may be detected), however, a study with monospecific serum to IgA will indicate a moderate amount of normal IgA and a significant amount of its defective monomers - heavy chains, which can be heterogeneous in electrophoretic mobility and molecular weight. Free a-chains, as well as their compounds, can be determined in duodenal contents, saliva, feces, urine.

Histological examination of a biopsy of the small intestinal mucosa reveals smoothing of the villi, compression of the crypts, infiltration of the proper layer by cells of varying degrees of plasmatization, in places by mature plasma cells, in places in the infiltrate there are cells that do not have clear signs of differentiation, in the cytoplasm of which crystalloid inclusions are found, the nature of which is not determined. Changes in the lymph nodes can be quite diverse: in the initial stage, the picture of reactive hyperplasia of lymphoid tissue with an increased number of plasma cells, later, with repeated biopsies, the pattern of follicles is lost, immunoblasts begin to predominate among small lymphocytes, which, against the background of proliferation of capillaries of the paracortical zones, creates a picture resembling angioimmunoblastic lymphadenopathy. Characteristic of this variant of lymphoma is the presence of peculiar cellular forms among lymphocytes, plasmablasts and immunoblasts, sometimes resembling Pirogov-Langhans, Sezary cells, and Berezovsky-Sternberg cells, which in some cases leads to erroneous diagnosis of lymphogranulomatosis or reticulosarcoma. The predominance of immunoblasts with obvious signs of nuclear atypia indicates the development of immunoblastic lymphosarcoma. In the mucous membrane of the small intestine and lymph nodes, intercellular amorphous or crystalloid inclusions characteristic of heavy chain disease are also determined, perceiving and not perceiving hematoxylin, having a positive PAS reaction.

Treatment of isolated forms of small bowel lymphoma involves excision of the tumor-affected segment within healthy tissues. However, the available experience in treating this disease indicates a significant therapeutic effect from long-term use of tetracycline for up to 1 year or more. If treatment is started at stage I of the disease, remission can be achieved over several years. The mechanism of this effect remains unclear. In addition, vincristine, cyclophosphamide, and prednisolone in combination with them are recommended. Long-term use of glucocorticoids alone does not cause remission.

When the disease progresses to the II "blast" stage, when the infiltration of the intestinal wall by lymphosarcoma cells extends to all layers, the risk of intestinal wall perforation and peritonitis increases. Generalization of the tumor to the peripheral lymph nodes dictates the need for an approach to treatment according to schemes intended for high-grade malignant lymphomas.

The course of the disease is accompanied by pronounced degenerative changes in the internal organs, contributing to the development of infectious complications (abscessing pneumonia, inflammation of the membranes of the brain, hemorrhagic syndrome), which are the causes of death.

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