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

With expressed dysplasia of lymphoid tissue and malignant lymphomas of plasmocyte differentiation monoclonal gammopathy is often noted. In this case, the nature of gammopathy, as a rule, corresponds to the plasma-cell secretion of the field on which lymphoma develops.

Among paraproteinemic hemoblastoses, selectively affecting the small intestine, the most common is Zeligmann's lymphoma, described by him and co-authors. In 1968. The names of this disease in the literature characterize its heterogeneous features: Zeligmann's lymphoma, intestinal form of heavy a-chain disease, primary lymphoma of the upper part of the small intestine, Middle Eastern lymphoma, Mediterranean lymphoma; on the nomenclature of WHO - "immunoproliferative disease of the small intestine".

Despite the detailed description of cases of a peculiar clinical and morphological picture, there are no established views on the etiology and pathogenesis of this lymphoma in the literature. The existing hypotheses are based on the possible role of prolonged local antigen stimulation of the small intestine by microorganisms in regions with a high incidence of intestinal infections, as well as on the genetic predisposition of patients, the effect of an oncogenic virus similar in structure to the gene controlling 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.

At the heart of the pathology is the primary disorganization in the B-cell lymphocytopoiesis system with characteristic excessive infiltration of the small intestine mucosa (less often the organs where IgA, nasopharynx, bronchi are also synthesized) by cells in which the pathological immunoglobulin is determined. Violation of protein synthesis is expressed in the complete absence of the molecule of light a- and beta chains of immunoglobulin in the construction of the defective heavy a-chains lacking the Fd-fragment. Similar changes are noted in the 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 to consider this disease as one of three immunochemical variants of heavy chain disease: a-chains (Zeligmann), much less common diseases of y-chains (Franklin) and ft-chains (Forte).

The first stage is characterized by symptoms of impaired absorption. Patients, complaining of a loose stool 10-15 times a day, abdominal pain, nausea, vomiting, these symptoms are noted several months before calling a doctor. Skin covers are pale, slightly flaky, the phenomena of acrocyanosis and pronounced exhaustion. Deficiency of body weight is 13-27 kg. Cervical, axillary and inguinal lymph nodes in some cases slightly increased. The liver is not enlarged. In single observations, the spleen is involved in the process with its insignificant increase. When palpation is determined soreness in all parts of the abdomen, more around the navel. The abdomen is swollen, the feeling of "testability" is at hand. The caecum is swollen with gases, rumbling and noise of splashing are heard. The chair is liquid, dark green up to 2500 g per day. In peripheral krovi - moderately severe anemia, thrombocytopenia up to 9x10 ¹¹ / l, the number of leukocytes varies (5.6-23.0x10 ¹¹ / l), depending on the inflammation that has joined. ESR accelerated to 25-54 mm / h. The amount of total protein is from 24.5 to 59.6 g / l; albumin - 40-45%; globulins: a1 - 3-4.5%, a2 - 12.3-22%, beta - 15-16.7%, y - 15-22.2%; potassium of blood -2,5-3,7; sodium - 120-126 mmol / l. When immunological examination of peripheral blood lymphocytes - a moderate decrease in the number of T cells and an increase in B-lymphocytes.

When X-ray examination against the background of enlarged folds of the jejunal mucosa, scattered numerous fuzzy, locally merging round and oval filling defects 0.5-0.8 cm in diameter creating nodularity of the relief are seen. In some places, the intestine can be spasmodically reduced, enlarged regional lymph nodes may form small impressions into the intestinal wall.

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

In the determination of immunoglobulins by the method of radial immunodiffusion, a decrease in IgG and IgM and a significant increase in IgA up to 4,400 x 10 ³ IU / l) may be observed , however, a study with monospecific serum to IgA will indicate a moderate amount of normal IgA and a significant number of its defective monomers - heavy chains, which can be heterogeneous in terms of 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 the biopsy specimen of the mucous membrane of the small intestine determines the smoothness of the villi, the compression of the crypts, the infiltration of the own layer by cells of different degrees of plasmatisation, sometimes the cells in the infiltrate have clear signs of differentiation, in the cytoplasm of which crystalloid inclusions are found whose nature is not determined. Changes in the lymph nodes can be very diverse: in the initial stage, the picture of reactive hyperplasia of lymphoid tissue with an increased number of plasma cells, then in the course of repeated biopsies the follicle pattern is lost, immunoblasts begin to predominate among small lymphocytes, which, in the background of proliferation of capillaries of the paracortical zones, creates a picture resembling angioimmunoblastnuyu lymphadenopathy. Characteristic for this variant of lymphoma is the presence among the lymphocytes, plasmablasts and immunoblasts of peculiar cellular forms, sometimes reminiscent of the cells of Pirogov-Langhans, Sesari, and Berezovsky-Sternberg cells, which in some cases leads to erroneous diagnosis of lymphogranulomatosis or reticulosarcoma. The predominance of immunoblasts with obvious signs of atypia of the nuclei indicates the development of immunoblastic lymphosarcoma. In the mucosa of the small intestine and lymph nodes, intercellular amorphous or crystalloid inclusions that are characteristic of heavy chain disease and those that perceive and do not perceive hematoxylin having a Schick-positive reaction are also determined.

Treatment for isolated forms of lymphoma of the small intestine involves the excision of a tumor-infected segment within healthy tissues. However, the existing experience of therapy of this disease indicates a significant therapeutic effect from prolonged - up to 1 year or more - the use of tetracycline. If the treatment is started at the first stage of the disease, then it is possible to achieve remission for several years. The mechanism of this effect remains unclear. In addition, vincristine, cyclophosphamide and, in combination with them, prednisolone are recommended. Long-term use of some glucocorticoids does not cause remission.

When the disease passes into the II "blast" stage, when the infiltration of the intestinal wall by the cells of lymphosarcoma extends to all layers, there is a growing danger of perforation of the intestinal wall and development of peritonitis. Genitalization of the tumor along the peripheral lymph nodes dictates the need for an approach to treatment according to schemes designed for high-grade lymphomas.

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

[1], [2], [3], [4], [5], [6]