Lymphoma

Concept. Lymphomas constitute a group of diseases characterized by a neoplastic proliferation of the lymphoreticular portion of the reticuloendothelial system, which fundamentally affects the cells of the lymphocytic and histiocytic series. Some authors use the generic term lymphoproliferative disorders.

Summary

[ disguise ]

• 1 Classification
• 2 Etiology
• 3 Frequency
• 4 Pathological anatomy
  • 1 Macroscopic appearance
  • 2 Microscopic appearance
• 5 Clinical picture
• 6 Complementary exams
• 7 Diagnosis
• 8 Forecast
• 9 Treatment
• 10 Source

Classification

There are numerous classifications that have been developed about these diseases from a histological point of view. Any of them can be useful, although some are so complex that they can lead to confusion. Following the general guidelines of this work, we offer a classification whose importance lies in its simplicity.

1. Lymphosarcomas (lymphocytic, lymphoblastic).
2. Reticular cell sarcoma (reticulosarcoma).
3. Giant follicular lymphoma.
4. Hodgkin’s disease:
   1. Lymphocytic predominance.
   2. Mixed cellularity.
   3. Nodular sclerosis.
   4. Lymphocytic depletion.
5. Burkitt lymphoma.

Etiology

The etiology of these malignant diseases is unknown. Researchers who support infectious or neoplastic etiology have worked in this direction without conclusive results. However, viral etiology is currently gaining interest due to animal studies and the acceptance that Burkitt’s lymphoma is caused by a virus.

Frequency

Lymphomas are more common in men than in women in a ratio of 2:1. Hodgkin’s disease occupies first place in terms of frequency, and usually occurs between the ages of 15 and 35, followed by lymphosarcoma and reticulosarcoma with its highest incidence between 30 and 70 years of age; although we must remember that all of them can occur at any time in life. The rest of the lymphomas are less common in our environment.

Pathological anatomy

Macroscopic appearance

In general, malignant neoplasms of lymph nodes are characterized by an increase in the volume of said nodes, except for Burkitt’s tumor, which has a very peculiar location, mainly at the level of the jaw. The color varies from gray to pink and often presents areas of necrosis. The consistency is variable and the amount of necrosis is of great importance. In addition to originating in the lymph nodes, these neoplasms occur, although rarely, in the stomach and small and large intestine.

Microscopic appearance

From the microscopic point of view there is loss of normal architecture, effacement of the lymph node sinus and infiltration of the capsule; The constitution will vary according to the type of lymphoma. In lymphoblastic lymphosarcoma there is a net predominance of young lymphocytes; in the lymphocytic, adult lymphocytes.

Reticulosarcoma is characterized by a large proliferation of atypical reticular cells, which present great polymorphism and a marked increase in the production of reticulin, which is demonstrated by special silver impregnation techniques. Giant follicular lymphoma is characterized by an increase in the size and number of germinal follicles, which occupy both the cortex and the medulla.

In Hodgkin’s disease the picture will vary according to the type being treated, although they will all have in common the presence of the Sternberg-Reed cell, an essential fact to make this diagnosis; The predominantly lymphocytic type is characterized by being made up of adult lymphocytes, histiocytes and few Sternberg-Reed cells; The mixed cellularity type presents, in addition to the lymphocytic elements, abundant Sternberg-Reed cells, polymorphonuclear neutrophils and eosinophils, fibrosis and areas of necrosis.

The nodular sclerosis type is characterized, in addition to the elements mentioned above, by a large proliferation of collagen tissue in the form of thick bands more than a micron thick, which sometimes circumscribe cellular nests; The lymphocytic depletion type is characterized by a marked decrease in the lymphoid elements of the lymph node and a net predominance of atypical reticular cells and Sternberg-Reed cells.
Burkitt’s tumor presents a macroscopic appearance similar to that of lymphosarcomas; Histologically it is very characteristic, since there is a replacement of the underlying architecture by cells that occupy an intermediate place between lymphocytes and reticulum cells; In addition, dispersion of voluminous fire-like histiocytes in the background of the indicated elements, which produces a picture that has been compared to a starry sky.

Clinical picture

The different varieties of lymphomas have symptoms and signs that are similar to each other. Generally, the initial symptoms consist of one of the following conditions:

1. Painless increase in volume of the cervical, axillary or inguinal lymph nodes, mainly.
2. General condition with asthenia, anorexia and weight loss.
3. Cutaneomucous pallor, pruritus and intense night sweats.
4. Prolonged fever without apparent cause.

When the process begins in the extranodal lymphoid tissue, the clinical picture will depend on the affected viscus.
lymphadenopathy. The lymph nodes are hard in lymphosarcoma, and elastic in Hodgkin’s disease. They are generally painless, superficial (cervical, axillary, inguinal) and/or deep (mediastinal, intra-abdominal), and of variable size; At first they are single and circumscribed, but later, when others appear, they tend to form true lymph node packages.

Mediastinal lymphadenopathy is manifested by symptoms and signs that depend on the compression and obstruction of the various structures found in that area; Thus, we can observe dysphonia, dysphagia, cyanosis, edema in the slave’s neck, etc. Intra-abdominal lymphadenopathy, for the same reason, can produce obstructive jaundice (adenopathy of the hepatic hilum), malabsorption syndrome (taking of mesenteric and chyliferous lymph nodes), obstruction of the inferior vena cava, etc.
Fever. It can occur in all types of lymphoma and is sometimes the most prominent symptom. It appears more frequently in Hodgkin’s disease and although undulating PelEbstein fever (febrile periods alternating with subfebrile periods) has been described as characteristic, in reality it takes any type.
Splenomegaly. Splenomegaly is of variable degree and can sometimes occupy a large part of the left hemiabdomen. The spleen has a firm consistency and the symptoms may be related to the large space it occupies in the abdominal cavity.

The increase in the size of this viscus can produce, due to an increase in its hemocatheteric function, exaggerated destruction of the formed elements of the blood: anemia, leukopenia and/or thrombocytopenia (hypersplenism).
Hepatomegaly. Moderate hepatomegaly and, occasionally, hepatocellular jaundice due to infiltration of the gland may be observed.
General manifestations. Asthenia, weight loss and sweating are possibly secondary to neoplastic hypermetabolism. They may constitute the first manifestations of the disease, although they generally occur in advanced periods of the disease.
Fur. These patients present cutaneous-mucous pallor, expression of a more or less intense anemia, constant in advanced cases, and in whose pathogenesis one of the following factors intervenes: insufficient production, hyperdestruction due to an enlarged spleen or due to the formation of antibodies against red blood cells. (autoimmune hemolytic anemia). In the latter case the Coombs test is positive.

Scratching lesions occur due to intense itching, the pathogenesis of which is not well clarified. Herpes zoster also appears relatively frequently in these patients, especially in those affected by Hodgkin’s disease.
Respiratory system. Pulmonary infiltration can manifest itself in various ways: atelectasis, unilateral or bilateral pleural effusion, and nodular or reticular lesions reminiscent of carcinomatous lymphangitis.
Digestive system. The parts of the digestive tract most frequently affected are the stomach, jejunum, ileum, cecum and rectum, which causes symptoms that are confused with the manifestations of carcinomas of these structures (hematemesis, melena, obstruction, etc.). When the mesenteric nodes are invaded they can be palpated. Obstruction of the chyliferos will be manifested by a malabsorption syndrome.
Osseous system. Bone invasion generally occurs late. It may manifest itself as a tumor or pain in the affected region. Radiologically, the lesions are osteolytic and less frequently osteoblastic; pathological fractures may occur.
Nervous system. Invasion and compression of peripheral nerves produce intense pain and motor disorders. Due to fractures and crushing of the vertebral bodies, spinal compression syndromes (paraplegia, sensory disorders and radicular pain) usually occur. Sometimes, spinal cord compression is not due to pathological fractures, but rather to infiltration of the meninges, which behaves like subepidural or epidural tumors.

Complementary exams

The clinical diagnosis will only be based on suspicion and we will be obliged to confirm it with the histopathological diagnosis.
Hemogram. Generally there is anemia with the characteristics already described. Eosinophilia and leukopenia are not constant findings. There may be thrombopenia and normoblasts in the peripheral blood, as an expression of marrow seizure by the disease. Invasion of the blood by malignant-looking cells can be observed in advanced stages. We repeat that the finding of pancytopenia may be the translation of hypersplenism.
Erythrosedimentation. It’s accelerated.
Protein electrophoresis. May show hypergammaglobulinemia. Decreased gamma globulin is usually a sign of poor prognosis.
Adenogram. The puncture of an affected lymph node and the study of the material by spreading it on a slide sometimes allows a positive diagnosis to be established.
Radiology. In the chest x-ray, mediastinal polycyclic images of lymphadenopathy can be found, as well as pulmonary effusions and infiltrations (infrequent). The bone survey will be able to detect osteolytic or osteoblastic lesions in the spine, pelvis, ribs, etc.

Lymphography is very useful, whether performed in the lower or upper limbs, to first specify the extent of the process, and subsequently the therapeutic result. The contrasted radiological studies required by the patient’s symptoms (stomach and debt, intestinal transit, colon enema, cavography, urogram, etc.) must be performed.
Lymph node biopsy. It constitutes the obligatory complementary investigation in all these processes and the one that will give us the definitive diagnosis.
Exploratory laparotomy. Exploratory laparotomy with splenectomy, abdominal lymph node resection and liver biopsy is currently being used to specify the stage of the process, after having made the diagnosis by lymph node biopsy.

Diagnosis

Lymphomas must be differentiated from those processes capable of producing a similar clinical picture: prolonged febrile syndrome, adenic syndrome, splenomegaly, etc. The positive diagnosis is established through lymph node biopsy, although vacuum puncture of a lymph node (adenogram) may be useful in some cases.

The medullogram will only be positive in some cases in advanced stages of the disease, so the diagnosis should not be based on this type of examination. Having already made the histological diagnosis of the disease, it is necessary to define the extent of the condition. For this we will use the physical examination, simple or contrasted radiological studies, lymphography and exploratory laparotomy.

Forecast

The modern therapeutic schemes applied in this disease have significantly improved its prognosis. In general, they have managed to prolong and make the patient’s life more useful, and there are even those who report cures in stages 1 and 2 of Hodgkin’s disease.

Treatment

The effectiveness of treatment depends largely on careful evaluation regarding the extent of the disease. Although the Peters classification was established for Hodgkin’s disease, it can also help us evaluate the clinical stage of all lymphomas. This classification places lymphomas in four evolutionary stages:

• Stage 1: Disease limited to a single nodal group or two contiguous groups, on one side of the diaphragm.
• Stage 2: Disease of two or more non-contiguous lymph node groups on one side of the diaphragm.
• Stage 3: Disease of lymph node groups on both sides of the diaphragm, but whose extension does not exceed the lymph nodes, spleen, Waldeyer’s ring, or more than one of these structures.
• Stage 4: Infiltration of the bone marrow, lung parenchyma, pleura, liver, bone, kidneys, digestive system or any tissue or organ in addition to the lymph nodes, spleen and Waldeyer’s ring.

In all stages there can be two subtypes:

• a) No symptoms
• b) With symptoms (fever, itching, night sweats).

As will be seen later, it is extremely important to make the distinction between two large groups of patients: those who are in stage 1 or 2 and those who are included in stages 3 and 4, since the therapeutic approach will be different.

Once the histological diagnosis of lymphoma has been established, sometimes a simple physical examination allows the patient to be classified or placed in stage 3 or 4. In these cases it is not necessary to continue with another type of investigation aimed at specifying the stage, since its result will not change. the therapeutic approach.

On the contrary, if the physical examination classifies them in stage 1 or 2, other means must be exhausted (radiology, lymphography, laparotomy) that can offer greater guarantees of a correct assessment of the stage in which they are found. Currently, some authors prefer in these cases to initially perform an exploratory laparotomy with splenectomy, resection of abdominal lymph nodes for histological study and liver biopsy. Once the extent of the process has been specified, the treatment can have two objectives:

1. For curative purposes. Patients in stages 1 or 2, with or without general symptoms.
2. For palliative purposes. Patients in stage 3 or 4.

In the first case, radiotherapy will be used and in the second, chemotherapy. Some authors are testing radiotherapy in stage 3, but the large extension of the areas to be irradiated causes the development of very severe complications. The great benefits that have been obtained with radiotherapy in stages 1 and 2 of Hodgkin’s disease have not been achieved in other types of lymphomas.

• Radiotherapy . It is the domain of the radiotherapist.
• Chemotherapy . For chemotherapy treatment, we have several cytostatics: nitrogen mustard, cyclophosphamide, vincaleucoblastine, vincristine, etc.

We must not forget that all these medications require very rigorous hematological control. If the leukocyte count drops below 3,000 per mm3, treatment, with the exception of prednisone, should be discontinued and wait a few days until the patient recovers. Sometimes this is not achieved, either because irreversible drug aplasia has occurred, or because hypersplenism has appeared.

In the latter case, splenectomy should be considered. On the other hand, blood must be administered every time the general condition of the patient requires it and infections must be vigorously treated, a frequent complication in these patients due to the immune deficiency that conditions this type of condition and due to treatment with cytostatics, which, like all We know, they are immunosuppressive.