Lymphosarcoma

LYMPHOSARCOMA, a malignant tumor of adenoid tissue, affecting both lymph nodes and all kinds of lymphoid formations of the lymphatic apparatus of various organs. This disease, which is sometimes difficult to distinguish from other hyperplasias of the lymph nodes, was studied by Virchow and received its name from him; many other names were subsequently proposed for it: adenia (Trousseau), lymphosarcoma malignum (Billroth), malignant lymphadenoma (Orth), pseudoleukemia (Cohnheim), and others. This abundance of names shows that isolating lymphosarcoma as a distinct pathological entity is very difficult, especially in view of the existence of transitional forms from lymphosarcoma to adjacent and in many respects similar systemic lesions of the lymphatic apparatus. The credit for clearly separating lymphosarcoma from the collective group of Cohnheim's pseudoleukemias belongs to Kundrat and Paltauf (Kundrat, 1893; Paltauf). According to their definition, lymphosarcoma is a malignant proliferation of lymphoid tissue, fully analogous to a malignant tumor. The proliferating masses of adenoid tissue possess aggressive growth, penetrate into neighboring tissues, which undergo atrophy and disappear under their pressure. Tumor elements are capable of producing true metastases, but mostly via lymphatic pathways, much more rarely via blood vessels. Thus, lymphosarcoma can become generalized, capturing ever new organs or areas of the body. It is highly probable that the involvement of various groups of lymph nodes, as well as the generalization of lymphosarcoma, does not always occur by way of metastasis. It is possible to think that more often it is a matter of multiple (systemic) origin of lymphosarcoma in various lymph nodes and lymph follicles scattered in different organs; for such cases, the term lymphosarcomatosis is appropriate. Usually, the disease begins with the swelling of a group of lymph nodes, most often the nodes of the neck, the axillary region, less often the nodes of the mediastinum, mesentery, retroperitoneum, and even more rarely the inguinal ones. In the initial stage, a small, painless tumor covered by unchanged skin can be felt. Soon it is discovered that the enlarging nodes have fused into a packet, because the proliferating cellular elements grow through the capsules of the nodes and spread to neighboring tissues. Due to this, the packet of nodes fuses with the surrounding muscles and skin, for example, in the neck or axillary region; primary tumors of the mediastinum spread to the lungs, grow around the pericardium and heart, and from the mesenteric nodes, they pass to the wall of the intestines, etc. By growing around large vessels of the thoracic cavity, the trachea, and the small intestines, the tumors can cause severe stenosis and dysfunction of these organs. The consistency of tumors in lymphosarcoma varies depending on the greater or lesser participation of the stroma. Initially, the tumors may be softer and harden later, similar to lymphogranulomas; or the tumor acquires a dense consistency from the very beginning, sometimes even a very dense, fibrous one. Soon after the appearance of the tumor, it is discovered that the swelling of the nodes has spread to new areas, involving new packets of lymph nodes in the hyperplasia; in this way, lymphosarcoma can capture very many groups of lymph nodes. Large tumor sizes are characteristic of lymphosarcoma, often reaching the size of an adult's head. Unlike leukemic lymphadenoses, lymphosarcoma usually does not cause general involvement of all lymph nodes or all adenoid tissue of the body. On the contrary, hyperplasia is often limited to one area or one side of the body, and then lymphosarcoma acquires a resemblance to ordinary round-cell sarcomas. The difference from them, besides the histological structure, also lies in the fact that banal sarcomas spread by metastasis primarily via blood vessels, whereas lymphosarcoma captures new and new groups of lymph nodes (see above). A feature of lymphosarcoma is also the circumstance that they can arise from any adenoid formation of the mucous membranes, e.g., in the tonsils, solitary follicles of the intestine, etc., and only secondarily spread to regional nodes. Finally, lymphosarcomas are prone to extensive softening (necrosis) and ulceration of the skin or mucous membrane covering the tumor. It is understandable that with a great variety of localizations of lymphosarcoma, their clinical manifestations are very different. Here, in particular, one should note the localization in the thoracic cavity, which gives symptoms of a rapidly growing tumor of the mediastinum or lung. To the phenomena of stenosis of the bronchi and large veins, esophagus, and trachea, disorders of cardiac activity from the tumor masses growing around the layers of the pericardial sac can be added. Growths of the tumor through the vertebrae into the spinal canal and compression of the spinal cord have even been observed. Affecting the cervical nodes, the process entails, due to the compression of the cervical vessels, sharp phenomena of congestion and edema in the area of the neck, chest, and face, sometimes passes to the pharynx and larynx, causing disorders of speech and the act of swallowing, as well as symptoms of stenosis of the esophagus and respiratory tract. Lymphosarcoma of the axillary and inguinal nodes gives symptoms of compression of vessels and nerves, causing, in addition to cyanosis and congestive edema of the chest, neck, or limbs, phenomena of hyper- and paresthesia, neuralgia, and neuritis, sometimes motor disorders (pareses and paralyses). In lymphosarcoma of the retroperitoneal and mesenteric nodes, symptoms of intestinal obstruction, ascites, etc., can be observed. A frequent localization of lymphosarcoma is the mucous membrane of the digestive tract; here the tumor causes early phenomena of narrowing (e.g., of the pharynx when localized in the pharyngeal adenoid ring) or phenomena of dilation at the site of the tumor in connection with its breakdown. Lymphosarcoma of the genital organs and skin is relatively rare. By the metastatic hematogenous route, the kidneys are often affected, in which tumors develop either as separate nodes or diffusely infiltrate the entire tissue, destroying the pattern of the kidney structure. It is necessary to note that lymphosarcoma extremely rarely affects the spleen and liver. This circumstance is an important differential distinction of lymphosarcomatosis from lymphogranulomatosis, in which, on the contrary, involvement of the spleen is very frequent and even specific, and granulomas in the liver are far from rare. Changes in the blood in lymphosarcoma are not characteristic. Almost always, a more or less pronounced anemia is observed. As for white blood cells, lymphopenia and a slight neutrophilic leukocytosis were most often noted. The number of lymphocytes is often sharply reduced, sometimes reaching 2-3%. A decrease in the absolute number of lymphocytes is a fairly characteristic sign for lymphosarcoma. In rare cases, lymphosarcomatosis proceeds with leukemic phenomena, on the basis of which it has been proposed (Pappenheim) to distinguish between leukemic and aleukemic lymphosarcomatosis. A number of authors (Naegeli, Frankel, Fabian, and others) even believe that lymphosarcomatosis, leukemia, and pseudoleukemia represent gradations of essentially one and the same process. The microscopic picture of lymphosarcoma is very characteristic. Not only lymphocytes but also the reticular stroma undergo multiplication. This feature of lymphosarcoma distinguishes it from ordinary round-cell sarcomas. Due to the participation of the reticular stroma in the neoplasm, the latter consists of lymphocytes lying in the loops of the reticular mesh stroma. It can remain a delicate network of crossbars, which is found in normal adenoid tissue of lymph nodes, or it can coarsen, with the crossbars of the network acquiring the character of thick homogeneous strands, or finally, the adenoid stroma metaplases into fibrous tissue. The amount of fibrous tissue is sometimes so great and predominant that lymphocytes infiltrate it in small groups or strips. Such tumors, understandably, possess great density. Their old sections can become so depleted of lymphocytes that they take on the character of dense fibromas and even macroscopically seem to be a fibrous mass of fascicular structure. On the contrary, in young, growing sections, lymphocytes predominate, embedded in a not yet coarsened stroma. It is necessary to note that the tumor cells of lymphosarcoma do not have the appearance of ordinary lymphocytes filling, for example, a lymph node. They are larger, their nucleus is poorer in chromatin, and of more diverse shape, which brings them closer to lymphoblasts; often there is also some polymorphism, atypia of tumor cells, which, in connection with the abundance of mitoses, indicates the malignant character of the neoplasm. In some cases, one can speak of polymorphic-cell, spindle-cell lymphosarcomatosis. The difference between tumor cells and normal lymphocytes of lymph nodes allowed establishing that the growth of the tumor occurs by displacing normal adenoid tissue, and not by involving it in hyperplasia, which was first pointed out by Ribbert. The diagnosis of lymphosarcoma is not always easy, especially at the beginning of the suffering. The exclusion of ordinary malignant tumors, carcinomas, and sarcomas is achieved without particular difficulties. In particular, nodes of lymphosarcoma, especially secondary ones, are distinguished from carcinosis of the lymph nodes by faster growth and relative softness. It is much more difficult to distinguish lymphosarcomatosis from aleukemic lymphadenoses, lymphogranulomatosis, tuberculous and syphilitic lymphomatoses, especially from pseudoleukemias and Sternberg's leukosarcoma.

In pseudoleukemia, a moderately aggressive growth of lymphocytes of the adenoid tissue is sometimes also detected, thanks to which they not only penetrate the capsules of the glands but infiltrate the surrounding cellular tissue, muscles, and thus it comes to the formation of lymph nodes fused into packets, and the overgrowth of veins and nerves. The distinction from such cases can only be the universality of adenoid hyperplasia in pseudoleukemia, the systemic nature of the lesion, whereas lymphosarcomatosis, no matter how widely it has encompassed the adenoid tissue of the body, remains a tumor with multiple metastases. Sternberg's leukosarcomatosis is similar to lymphosarcomatosis in that it begins with local swelling of the glands and only later encompasses many regions of adenoid tissue, and moreover, as Sternberg asserts, by way of metastasis of tumor elements; the distinction of leukosarcomatosis is the leukemic blood picture typical for leukemias, which is almost never observed in lymphosarcomas (see above). For the latter, it is characteristic for tumors to arise from the mucous membrane (from its lymph nodules), for example, of the pharynx or from some lymph gland, rapid growth, its infiltrative character with the fusing of affected glands into large, immobile packets, the frequency of tumor localization in the mediastinum, where it rapidly overgrows its organs, and finally, incomplete generalization to other regions; on the contrary, pseudoleukemic tumors are distinguished by the fact that they seize all the lymph glands of the body and remain soft. The spleen, which constantly participates in hyperplasia in lymphadenosis, is almost never involved in lymphosarcomatosis. Nevertheless, it must be said that distinguishing lymphosarcomatosis from aleukemic lymphadenosis is difficult not only clinically, but even by way of excision and biopsy, so similar are both processes to each other in microscopic pictures. L. differs from lymphogranulomatosis by the absence of characteristic fever, itching, neutrophilic leukocytosis, or eosinophilia; often only a biopsy has decisive significance (see Lymphogranulomatosis); however, in the early periods of the disease, significant difficulties are possible here as well. The etiology of L. is unknown. Some authors are inclined to link it with tuberculosis; however, on the one hand, the combination of L. with tuberculosis is quite rare, and on the other hand, tubercle bacilli can be found in glands during various pathological processes in them without an etiological connection. Cases of familial disease of L. have been described (Braun). An interesting question is the infectious nature of L., which cannot be considered solved. Lymphosarcomatosis affects all ages, but is especially often encountered in the mature age (from 15 to 30 years), in men more often than in women; its course is usually quite rapid, although cases have been described in the literature where tumors decreased and disappeared spontaneously or after the excision of test pieces, but subsequently recurred and in the end led to death. L. proceeds without temperature, sometimes only giving slight rises. Disorders of a general nature have somewhat less significance in the symptomatology of L. than in cancer, sarcoma, and other malignant tumors. The rapid growth of the process affects the function of organs important for life so early and substantially that patients sometimes perish before the appearance of general phenomena (cachexia, anemia). According to Kundrat's observations, the malignancy of L. exceeds the malignancy of cancers and sarcomas. However, there are also less malignant cases in which a temporary regression of tumors occurs after ulcerous decay and scarring; however, they continue to grow in their other sections. Thus, there are two varieties of lymphosarcomas: malignant and relatively benign. Microscopically, they are completely similar to each other. According to data from Moscow prosectoriums for 1923-27, lymphosarcomas constitute 24.3% of all sarcomas and 1.8% of all malignant neoplasms.

F. Chistovich, O. Makarovich. The treatment of L. can be surgical and therapeutic. Regarding the advantages of one method or the other, there is no definite opinion. Rapid recurrences, a poor prognosis, and mainly the absence of other more reliable methods of treatment compel one to decide on surgical intervention in the initial stages. The latter has the goal of removing the entire tumor with the surrounding tissues already involved in the process by the moment of the operation. The best results are obtained with the surgical removal of superficially located tumors. The situation is completely different with L. of the mediastinum, the gastrointestinal tract, the retroperitoneal space, etc., which are diagnosed in late stages when radical surgical intervention is no longer feasible, and even if it is feasible, it does not lead to the goal, since recurrences appear very quickly. The presence of metastases, which should be sought even in the early stages of the disease, is a contraindication to any surgical intervention whatsoever. In general, it should be emphasized that the operation does not eliminate the disease, and the tumor appears in ever new places. Poor long-term results after surgical treatment gave H. Küttner reason to recommend in 1922 that all L. be treated with X-rays. For L. that are not amenable to surgical treatment, one should use conservative measures, among which the first place should be given to treatment with X-rays and radium. Treatment of L. with radiant energy is reduced mainly to X-ray therapy. Radium has been little tested here and is rarely applicable in view of the usually large sizes of the tumors. It is believed that tumor cells are destroyed by radiant energy similarly to the less resistant lymphocytes located in lymph glands. X-ray therapy gives especially good results in L. of the pharynx; the tumor in this type of treatment sometimes disappears extremely quickly. A temporary but good effect from X-rays is even considered characteristic for L. It is recommended to combine X-ray therapy with large doses of arsenic. However, long-term results are less encouraging in view of frequent recurrences and metastases. A contraindication to X-ray therapy is pronounced cachexia and anemia, especially in the presence of large tumors, the rapid decay and absorption of which after irradiation can cause severe, and sometimes fatal, intoxication. As for other conservative methods, such as treatment with arsenic, iron, iodine, encytol, salvarsan, as well as protein, serum, and toxin therapy (according to Coley), they are calculated for a general effect and provide serious service only in combination with X-rays and radium. Still, it is necessary to note the special significance of intensive arsenic treatment. In general, almost all authors note that modern methods of treating lymphosarcoma give discouraging results.