LYMPH NODE ASPIRATION
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1 LYMPH NODE ASPIRATION CLINICAL AND HEMATOLOGIC OBSERVATIONS IN 11 PATIENTS* MAURICE MORRISON, M.D., A. A. SAMWICK, M.D., JOSHUA RUBINSTEIN, M.D., MELVIN STICH, M.D., AND LEO LOEYVE, M.D. From the Jewish Hospital of Brooklyn, the Jeioish Sanitarium and Hospital for Chronic Diseases, the Beth El Hospital and the Brooklyn Cancer Institute, Brooklyn, A T eio York Lymph node aspiration has become an important adjunct to the study of lymphadenopathies. 1 ' 3 " Si 8> 1 The procedure is of great value for the diagnosis of Hodgkin's disease, lymphosarcoma, leukemia and infectious mononucleosis. An aspiration may be repeated at intervals thus furnishing a guide to the effect of treatment. This procedure may also obviate the necessity of surgical excision of a node for biopsy. The most detailed recent study of the subject is the treatise by Tage Strange of Copenhagen. 9 The present report is based on our experiences in 11 patients with biopsy of tissue aspirated from lymph nodes. MATERIAL AND METHODS The diagnoses are indicated in Table 1. In addition to lymph node aspiration, other studies included those of peripheral blood and bone marrow, biopsy of splenic tissue obtained by puncture 6 or surgical removal of the spleen, and of surgically removed lymph nodes, and necropsy. The apparatus required includes a 2-gauge needle, a dry syringe and an alcohol sponge. No anesthetic is necessary. The operator grasps the node securely between the thumb and index finger of the left hand. He pierces the node, aspirates the tissue rapidly and then promptly withdraws the needle. He then makes a smear of the aspirate on a clean slide for staining with Wright's stain. ILLUSTRATIVE CASES 1. Myelogenous leukemia. (Fig. 5). A. B., a woman, age 5, was admitted to the hospital with pallor, fever, extreme adenopathy and ascites. The spleen extended four fingerbreadths below the left costal margin and the liver, three fingerbreadths below the right costal margin. The clinical picture favored a diagnosis of chronic lymphatic leukemia or Hodgkin's disease because of the collar of enlarged lymph nodes about the neck and the extreme enlargement of the nodes in the cervical, axillary and inguinal regions. The peripheral blood study determined the true nature of the process and tissue aspirated from the lymph node and spleen was confirmatory. The unusual feature was the striking lymph node involvement in a patient with myelogenous leukemia in a pre-agonal state. 2. Chronic lymphatic leukemia. (Figs. 3 and 4). A. G., a woman, age 62, represented a typical instance of chronic lymphatic leukemia in an older person. The lymphoblasts were prominent with a predominance of Grumel6e cells. This feature usually indicates either that the patient is entering an acute phase, or that x-ray therapy has induced in the patient a tendency to lymphoblastic "left shift". The presence of the Grumel6e cell serves to eliminate the diagnosis of lymphosarcoma. At times, this distinction is difficult. It may be stated that, as pointed out by Strunge, the characteristic Grumel<5e cell is present in pre- * Aided by a grant from the Jacques Loewe Research Foundation, New York, New York. Received for publication, July 19, Downloaded from on 11 May 218
2 256 MORRISON ET AL. ponderant numbers only in lymphatic leukemia. In acute lymphatic leukemia or after radiation therapy, lymphoblasts with characteristic nucleoli overshadow the presence of Grumel^e cells. 3. Lymphosarcoma. (Fig. 2). M. Y., a woman, age 39, was admitted with pallor and ecehymoses. On examination, lymphadenopathy and an enlarged spleen were found. The peripheral blood showed no evidence of the disease. The bone marrow showed an eosinophilia of 1 per cent. The latter finding suggested the possibility of Hodgkin's disease but the lymph node aspirate revealed the presence of lymphosarcoma cells. A biopsy had resulted in a diagnosis of lymphadenitis. In view of this discrepancy, the pathologist reviewed the original section and found evidence in it of lymphosarcoma. 4. Giant follicular lymphoblastoma. M. A., a woman, age 53, was admitted to the hospital because of enlarged axillary and inguinal nodes. Lymph node aspiration revealed cells suggesting lymphosarcoma. Biopsy of a lymph node showed giant lymphfollicular lymphoblastoma. TABLE 1 DIAGNOSES IX 11 PATIENTS FROM WHOM LYMPH NODE TISSUE WAS ASPIRATED LEUKEMIA Acute myeloblastic 3 Chronic myelocytic 1 Monocytic 2 Chronic lymphatic 19 Chronic lymphatic, terminal (acute phase) 1 Stem cell 1 ' -LYMPHOSARCOMA Lymphosarcoma (small cell type) 12 Follicular lymphoblastoma 2 HODGKIN'S DISEASE 15 METASTATIC CANCER 7 INFECTIONS Tuberculosis 3 Boeck's sarcoidosis 1 Hepatitis, infectious 1 Infectious mononucleosis 5 Lymphadenitis 11 ANEMIAS Congenital hemolytic icterus 1 Cooley's anemia 1 MISCELLANEOUS CONDITIONS Lipoid dystrophy 1 Chondroma 1 Cirrhosis of liver 1 ASPIRATED TISSUE INADEQUATE FOR DIAGNOSIS Hodgkin's disease. (Fig. 1). S. D., a man, age 35, was admitted to the hospital with pain in the chest, fever, and generalized adenopathy. A lymph node aspiration revealed evidence of Hodgkin's disease, i.e., Reed-Sternberg cells, monocytoid cells, pleomorphism and eosinophilia. Some time later a biopsy confirmed the diagnosis. 6. Metastatic cancer. (Figs. 7 and S). A: B., a woman, age 64, was admitted to the hospital because of carcinoma of the breast with axillary nodes. Lymph node aspiration confirmed the diagnosis. All figures were made from material aspirated from lymph nodes. FIG. 1 (upper left). Dorothy-Reed cell in Hodgkin's disease. X 98. FIG. 2 (upper right). "Lymphosarcoma" cell (Patient M. Y.). Notice large cells with scant cytoplasm. These do not have appearance of Grumel<5e cells. X 13. FIG. 3 (lower left). Grumel(5e cell from Patient A. G. with chronic lymphatic leukemia. Note checkerboard appearance of nucleoplasm and occasional lymphoblast. X 13. FIG. 4 (lower right). Patient A. G. with chronic lymphatic leukemia. Grumel6e cell, enlarged. X 3. Downloaded from on 11 May 218
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4 258 MORRISON ET AL. 7. Infectious mononucleosis. (Fig. 6). E. L., a male college student, age 19, was admitted to the hospital with two months' history of enlarged firm, nontender, discrete nodes in the cervical, axillary, inguinal and occipital regions. There was no evidence of enlargement of the nodes in the mediastinum. The liver and spleen were not enlarged. Cells suggestive of infectious mononucleosis were seen in the peripheral blood and in tissue aspirated from a node. 8. Lymphadenitis. B. S., a man, age 59, was admitted to the hospital with an enlarged cervical lymph node. The liver and spleen were foundto be enlarged. Clinically a diagnosis of Hodgkin's disease was suggested. The peripheral blood and bone aspiration'were noncontributory. Biopsy of a lymph node showed lymphadenitis, an occasional polymorphonuclear neutrophil, but no lymphoblasts, Crumel<?e or Reed-Sternberg cells. DISCUSSION. Progress has been made within recent years in developing methods for the diagnosis of a number of blood dyscrasias. In Hodgkin's disease, lymphosarcoma, giant follicular lymphoblastoma, and metastatic cancer in the nodes, often no definite diagnosis can be made on hematolqgjc.yfindings. At times the answer is found only on biopsy or necropsy. Lymph-node aspiration is therefore a helpful diagnostic method. In addition, certain instances of infectious mononucleosis difficult of diagnosis and leukemia are recognized after study of tissue aspirated from a lymph node. Some conditions, such as tuberculosis, Boeck's sarcoidosis and metastatic cancer require further experience with the method of biopsy of tissue aspirated from lymph nodes. ' - As will be noted in Table 1, approximately SO per cent of the patients studied had leukemia, lymphosarcoma, Hodgkin's disease;' lymphadenitis or metastatic cancer. There were also 5 patients with infectious mononucleosis and 3 with tuberculosis. Five of the patients were children, the youngest being four months old and the oldest eight years old. Table 2 offers a brief description of the cell type; the frequency of occurrence and the specific condition where these cells are found. Based upon the morphologic character of these elements, we set down tentative hematologic criteria for lymph node aspiration in different conditions (Table 3). In Table 4, one notes that lymph node aspiration provided the means for making the correct diagnosis most often in Hodgkin's disease, lymphosarcoma, lymphadenitis and metastatic cancer. In contrast, study of the peripheral blood alone was diagnostic in' lymphatic leukemia and infectious mononucleosis. In our study, information was obtained by concomitant aspirations of the spleen in 15 of 19 patients with lymphatic leukemia, in each of our 12 patients with lymphosarcoma, in three of our 15 subjects with Hodgkin's disease and in one of our patients with giant follicular lymphoblastoma. The question arises: will the diagnosis sometimes be overlooked in biopsy of FIG. 5 (upper left). Patient A. B. with myelosis of lymph node in late chronic myelogenous leukemia. Note myelocytes and myeloblasts. X 1. FIG. 6 (upper right). Patient A. W. Large cells of infectious mononucleosis. X 25. FIG. 7 (lower left). Clusters of malignant cells within a lymph node. X 55. FIG.-8 (lower right). Same as Figure 7. X 11. Downloaded from on 11 May 218
5 FIGS. 5-S 259 Downloaded from on 11 May 218
6 26 MORRISON ET AL. aspirated tissue when the conventional biopsy would be more revealing? We have never found this to be true. The same objection was raised in 1938 concerning the feasibility of biopsy of aspirated bone marrow as compared to that of biopsy of trephined bone marrow. 2 In time, it was found that each method has its place. Furthermore, bone marrow aspiration has become almost indispensable in hematology. We predict that similarly lymph node aspiration will prove of great value in replacing or supplementing surgical biopsy in the hematologic study of the TABLE 2 DESCRIPTION OF CELL TYPES NOTED IN TISSUE ASPIRATED FROM LYMPH NODES CELL TYPE FREQUENCY OCCURRENCE DESCRIPTION 1. Small lymphocvte 2. Large lvmphocvte 3. Reticulum cell 4. Syncytial cell 5. llcmoeytoblast 6. Grumelee cell* 7. Lymphoblast 8. Infectious mononucleosis cell. Myeloblast 1. Monocytoid cell 11. Ervthroid elements S5% 15% Many Many Many Many Normal Normal Inflammations, lymphosarcoma Lymphatic leukemia Normal and inflam-. mations Infectious mononucleosis Myeloses Hodgkin's disease Extramedullar}' hematopoiesis; spent polycythemia; osteosclerotic anemia Same as peripheral blood Same as peripheral blood Large nucleus (2-3 times size of small lymphocyte) surrounded by irregular cytoplasmic processes Groups of reticulum cells in masses with a common bluish cytoplasmic background Large cell (4-5 times size of small lymphocyte) with large nucleus of fine texture with one or more nucleoli, surrounded by a deep basophilic cytoplasm (forerunner of lymphoid series) Lymphoid elements with "checkerboard" nucleus Lymphoid elements with nucleoli Large lymphoid elements with indented nucleus and bluish cytoplasm Same as peripheral blood Like monocytes in peripheral blood, occasionally with more than one nucleus Reed-Sternberg cells Same as peripheral blood and bone marrow * The term "Grumelee" is freely used by Tage Strunge in his monograph. 9 It is taken from the French language and literally means "clotted". It applies to a cell with a lymphocytic nucleus of mosaic appearance and a "checkerboard" configuration. lymphadenopathies. At any rate, cytologic study of material aspirated from the lymph node is meant to be an adjunct and not a substitute for histologic study. It is easier to convince a patient to have an aspiration for cytologic study or biopsy than to have him submit to the conventional surgical removal of a lymph node for biopsy. SUMMARY Lymph node aspiration is a relatively simple procedure and can often be repeated either for subsequent study or in determining the effect of treatment. Downloaded from on 11 May 218
7 LYMPH NODE ASPIRATION 261 TABLE 3 CHARACTERISTIC FINDINGS IN TISSUE ASPIRATED FROM LYMPH NODES I. HODGKIN'S DISEASE A. Dorothy Reed-Sternberg cells B. Increase in monocytoid cells C. Eosinophils D. Polymorphonuclear neutrophils (1 to 5 per cent) E. Increase in large lymphoid cells. Ratio of small to large (S:L) lymphoid cells is 3:7 (normal S:L, 9:1). Reticulum cells II. LYMPHOSARCOMA A. Large lymphoid cells increased (S:L, 1:9). These cells have large nuclei, rare nucleoli and scant cytoplasm (no "checkerboard" appearance). B. Mitotic figures prominent C. hemocytoblast 111. LYMPHATIC LEUKEMIA A. Chronic 1. Small lymphoid cells (Grumel6e cells) increased (S:L, 9:1). These cells are medium-sized and have a "checkerboard" appearance. 2. Large lymphoid elements (rare) 3. No polymorphonuclear neutrophils B. Acute 1. Few Omnicide cells 2. Preponderance of lymphoblasts with nucleoli 3. Rare mitotic figure C. Subacute 1. Grumelde cells and lymphoblasts equal in number lv. r MYELOGENOUS LEUKEMIA A. Chronic, myelocytes (9 per cent of the cells) B.' Acute, myelocytes (9 per cent of the cells) V. LYMPHADENITIS, IRRITATIVE A. Ratio of small to large lymphoid elements (S:L, S:2) B. Moderate number of polymorphonuclear neutrophils C. hemocytoblast D. Rare eosinophil VI. LYMPHADENITIS, INFECTIOUS (PURULENT) A. Many polymorphonuclear neutrophils, degenerated, "toxic" B. Many smudged cells VII. INFECTIOUS MONONUCLEOSIS A. Large cells with indented nucleus and abundant basophilic cytoplasm B. Lymphoblasts (rare) C. No polymorphonuclear neutrophils VIII. NODE WITH METASTATIC CANCER A. Clusters of atypical cells B. Mitotic figures IX. GIANT FOLLICULAR LYMPHOBLASTOMA (Same as lymphosarcoma with addition of occasional monocytoid and small lymphoid cells) TABLE 4 COMPARATIVE DIAGNOSTIC VALUE OF STUDIES OF PERIPHERAL BLOOD, BONE MARROW AND LYMPH NODE ASPIRATION IN PATIENTS WITH LYMPHADENOPATHY NO. OF BLOOD STUDIES PER CENT OK CORRECT DIAGNOSES NO. OF BONE MARROW STUDIES PER CENT OF CORRECT DIAGNOSES NO. OF LYMPH NODE STUDIES PER CENT OF CORRECT DIAGNOSES Hodgkin's disease Lymphosarcoma Infectious mononucleosis Lymphadenitis Metastatic cancer Lymphatic leukemia S3 SO Downloaded from on 11 May 218
8 262 MORRISON ET Ah. Aspiration of material from enlarged lymph nodes will often provide diagnostic hematologic data in Hodgkin's disease, lymphosarcoma, lymphadenitis and metastatic cancer. A description is given of type cells encountered in material aspirated from enlarged nodes. Criteria are given for the diagnosis of enlargement of lymph nodes, based on cells found in the aspirate. REFERENCES 1. BOVER, G. F.: El Diagnostico por la Punsion Ganglionar. Valencia: Editorial Sabre, CUSTEH, R. P.: An Atlas of the Blood and Bone Marrow. Philadelphia: W.B.Saunders Company, 1949, p FORKNER, C. E.: Material from lymph nodes of man. Studies on living and fixed cells withdrawn from lymph nodes of man. Arch. Int. Med., 4: , MARTIN, H. E., AND ELLIS, E. B.: Biopsv bv needle puncture and aspiration. Ann. Surg.; 92: , MARTIN, H. E., AND ELLIS, E. B.: Aspiration biopsy. Surg., Gynec. and Obst., 59: , MORRISON, M.: An analysis of the blood picture in 1 cases of malignancy. J. Lab. and Clin. Med., 17: , MORRISON, M., SAMWICK, A. A., RUBINSTEIN, J., MORRISON, H., AND LOEWE, L.: Splenic aspiration. J. A. M. A., 146: , PAVLOVSKY, A.: La Ponction Ganglionar: Su Conticucion al Diagnostico Clinicoquirurgico de las Affeciones Ganglionares. Buenos Aires: Thesis, 1934, 82 pp. 9. STRUNGE, T.: La Ponction des Ganglions Lymphatiques. Copenhagen: Ejnar Munksgaard, 1944, 137 pp. 1. TEMPKA, T., AND KUBICZEK, M.: Normal and pathological lymphadenograin in the light of own research. Acta med. Scandinav., 131: , Downloaded from on 11 May 218
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