197 alcoholic with a "skid-row" drinker or with a psychopath will think it possible that he himself could have this condition. Instead of asking for help he may treat himself with tranquillisers or even barbiturates, and often become dependent on them as well. Alcoholism is the responsibility of a multidisciplinary team, but doctors’ clear acceptance of the alcoholic as a sick person worthy of needing help would in time lessen the stigma and encourage alcoholics and their families to ask for assistance much earlier. But fear of rejection often keeps alcoholics away from their G.P. Similarly, the alcoholic doctor himself feels ashamed of his "weakness" which he "should" be able to control. The covering-up by colleagues, rightly criticised by Dr Edwards and Dr Shribman (Jan. 10, p. 88), only serves to increase the risk to the alcoholic doctor and to his patients. Once the alcoholic doctor faces up to his problem the prognosis is usually good. Those doctors unable or unwilling to avail themselves of the extremely valuable services of Alcoholics Anonymous, the "self-help" alcoholic doctors’ group (which now has 80 members); should be of great value.2 not
St Bernard’s
Renal Unit,
Hospital,
Southall,
M. M. GLATT
Middlesex.
CIRRHOTIC GLOMERULONEPHRITIS AND SECRETORY IMMUNOGLOBULIN A
SiR,—Hyperglobulinxmia is a well-established feature of alcoholic liver cirrhosis, but the origin and the nature of this increased immune response is unknown. Callard et a1.3 found glomerular lesions in nine out of ten cirrhotic patients they investigated. The glomerulonephritis was characterised by the presence in the glomerulus of IgA, often associated with other immunoglobulins and C3. We have investigated twenty-two patients with proven alcoholic cirrhosis and compared them with twelve healthy subjects. Proteinuria was present in six patients with liver cirrhosis. Using discontinuous sucrose-gradient ultracentrifugation and reduction-alkylation of the immunoglobulins, we were able to measure serum monomeric and dimeric IgA levels along with IgM, IgG, and IgA-bound secretory component. By comparison with the controls, the cirrhotic patients presented the following increases of immunoglobulin concentrations: dimeric IgA 7.28 fold, monomeric IgA 2 41 fold, IgM 1.84 fold, IgG 1.56 fold, and IgA-bound secretory component 6.0 fold. As IgA and IgA-bound secretory component increased the most, we suggest that either IgA itself, originating from the gut, or its complex with bacterial, viral or dietary antigens, is deposited in the kidney and induces renal failure. IgA glomerular deposits in some cases of primary glomerulonephritis4 also probably have a mucosal, respiratory, or digestive, origin. Unite de Recherches de Physiopathologie
Digestive, INSERM U 45, Hôpital Edouard Herriot, Pavilion H,
A 42-year-old woman was referred for assessment of hypertension which had developed during her fourth pregnancy. Immediately after delivery the blood-pressure was 200/130 mm Hg lying and 160/120 mm Hg standing. At the same time creatinine clearance was 40 ml/min but rose after 2 weeks to 80 ml/min and has remained stable. An intravenous pyelogram and ultrasound evaluation were compatible with right-sided multicystic disease. The left kidney was elongated, with a duplex collecting system, but otherwise normal. Serum-IgA was undetectable. Blood-pressure was reduced to 150/90 mm Hg lying and standing with guanethidine 100 mg, clonidine 0-3mg, and spironolactone 50 mg daily. There was no past history of sinopulmonary infections, atopy, or use of the contraceptive pill. During follow-up for 20 months serum-IgA has remained undetectable, and the renal impairment has been stable. I wonder if the combination of hypertension, multicystic renal disease, and IgA deficiency is fortuitous or represents a genetic defect in this woman. I would be interested to learn of other cases.
FRANÇOISE ANDRÉ CLAUDE ANDRÉ
69374 Lyon, France.
IgA DEFICIENCY, HYPERTENSION, AND MULTICYSTIC RENAL DISEASE
Royal Infirmary,
ROGER GABRIEL
Hull.
ULTRASOUND AND SAFETY
(Oct. 18, p. 770) that the used in connection with the effect of ultra"mutagenic" sound on purified D.N.A. (Oct. 4, p. 662), is inappropriate, but we are not convinced by Dr Thacker’s other criticisms of our work. He argues that we have ignored evidence that does not support our recommendation to minimise ultrasound exposure of fetus. He maintains that degradation arises from hydrodynamic shear forces set up around oscillating or collapsing gas bubbles, but goes on to say that "to generate comparable shear forces in tissue a higher intensity would be required than that which degrades D.N.A. in solution, and were these forces sufficient to disrupt D.N.A. in chromosomes it is likely that damage to other cellular structures will be extensive enough to cause cell disruption and death." Hill’has pointed out that cavitation would happen in the liquid state but probably not in organised tissues, so we tried to work in conditions-frequencies of 2MHz and 0-87 MHz, volume of 7 ml, ambient pressure 1 bar, temperature below 25°C--below the cavitation threshold.3 The mechanism involved in the D.N.A. breaks we have observed is thus not clear. Hill has suggested that ultrasound could produce biological responses directly. The repeated vibrations, transmitted to the long, thin D.N.A. molecules, might produce shearing, and this mechanism might occur in vivo where cavitation is supposed not to happen. We have discussed these points elsewhere,4 taking into account Dr Thacker’s own review.5 We doubt whether cell disruption and death will necessarily happen before D.N.A. shearing. D.N.A., being the longest molecule in living cells, is therefore the most sensitive to shearing. Besides chromosome breaks happen at higher ultrasound intensities (in the W/cm2 range) :6-8 D.N.A. is sheared yet the cells are not dead. The presence of chromosome breaks rather than chromatid breaks means that the cells were sonicated at G,, and later went on to cell division. In our experiments we found that the intensities and durations necessary to break purified D.N.A. were uncomfortSm,—We
agree with Dr Thacker
term
SIR,-Your leading article
on selective IgA deficiency-’ report a patient with hypertension, multicystic renal disease, and absent serum-IgA, but with normal concentrations of IgM and IgG.
prompts me
to
1. Hill, C. R. J. acoust. Soc. Amr. 1972, 52. 667. 2. Hill, C. R. in Ultrasound in Clinical Diagnosis (edited by P. N. T. Wells); p. 165. Edinburgh, 1972. 3. Iernetti, G. Acustica, 1971, 24, 191. 4. Galperin-Lemaître, H., Kirsch-Volders, M., Levi, S. Humangenetik, 1975,
29, 61. 2 Glatt, M M. Lancet, 1975, i, 219. 3 Callard, P., Feldmann, G., Prandi, D., Belair, M. F., Mandet, C., Weiss, Y., Druet, P., Benhamou, J. P., Bariety, J. Am. J. Path. 1975, 80, 329. 4 Berger, J. Transplant Proc. 1969, 1, 939. 5 Lancet, 1975, ii, 1291.
5. Thacker, J. Curr. Topics Rad. Res. 1973, 8, 235. 6. Fischman, H. K., Coleman, D. J., Lizzi, F. L. J. Cell Biol. 1972, 55, 74a. 7. Slotova, J., Karpfel, Z., Hrazdira, I. Biol. Plant. 1967, 9, 49. 8. Coakley, W. T., Hugues, D. E., Slade, J. S., Laurence, K. M. Br. med. J. 1971, ii, 501.
198
ably close to the doses used in medical practice. As long as we remain ignorant of possible in-vivo effect on D.N.A. of ultrasound at medical doses, care should be taken when using sonication medicine, and uncontrolled peaks of high intensity should be avoided. Medical Genetics, Free University of Brussels, Faculty of Medicine, 97 rue aux Laines, 1000 Brussels, Belgium.
H. GALPERIN-LEMAITRE
Gynaecology and Obstetric Clinic, Brugmann University Hospital, Brussels.
S. LEVI
Crozer-Chester Medical Center,
IMMUNOBLASTIC LYMPHADENOPATHY ASSOCIATED WITH PHENYTOIN
(DIPHENYLHYDANTOIN) SIR,-Lukes and Tindle1 noted a frequent association of im-
lymphadenopathy (I.L.) with drug treatment, incase, diphenylhydantoin (’Dilantin’). Since there is a possibility that this lymphoproliferative process may be induced by chronic antigenic or drug stimulation, recognition of potentially provocative agents is important. We, too, have seen a patient who developed 1.L. while taking dilantin. A 78-year-old Black woman complained of fatigue and night
munoblastic
cluding,
in
one
She had arteriosclerotic cardiovascular disease and a seizure disorder requiring dilantin anticonvulsant therapy. Massive diffuse lymphadenopathy and hepatosplenomegaly were prominent physical findings. Her condition deteriorated rapidly over several weeks, despite stopping dilantin. Laboratory investigations showed: haemoglobin 10 g/dl; white blood-cell count 15 850 per mm3, with a predominance of reactive lymphocytes, plasmacytoid lymphocytes, and immunoblastic cells; platelet-count 72 000 per mm3; uric-acid 22 mg/dl; serum-protein electrophoresis 9.4 g/dl gammaglobulin, with a broad-based biclonal peak; quantitative immunoglobulin analysis showing two monoclonal proteins of kappa IgG’ and kappa IgA type (protein analysis performed by Dr Bias Frangione); direct Coombs test weakly positive; cryoglobulins and cryofibrinogen negative; Venereal Disease Research Laboratories and fluorescent-treponemal-antibody tests positive ; heterophile antibodies 1/28; positive rheumatoid factor; cold agglutinins 1/128. Lymph-node biopsy showed the angioimmunoblastic proliferation characteristic of i.L. Our diagnosis and slides were kindly reviewed and confirmed by Dr Henry Rappaport. Bonemarrow revealed lymphoproliferation consistent with i.L. This rapidly progressing and disabling disease was not influenced by discontinuing dilantin for 2 weeks, but physical findings and results of laboratory tests began to improve a few days after starting chemotherapy (cyclophosphamide, vincristine, prednisone) and were nearly normal after 2 months of observation and treatment. Prophylactic penicillin was also given because of serological evidence of syphilis. The patient died unexpectedly, apparently of her cerebrovascular disease, 2 months after starting treatment and 1 month after obtaining a clinical remission of her 1.L. At necropsy, I.L. was not apparent on external examination but was manifested by prominent lymph-node involvement, with abundant fibrosis and interstitial eosinophilic material, depletion of normal cells, and proliferation of vessels and plasmacytoid cells. Bone-marrow and spleen contained minor changes possibly related to 1.L. Cause of death was not established but was most likely related to her severe cardiovascular disease. No evidence of syphilis was found. This case illustrates’ the clinicopathological features of !.L. in a patient taking dilantin anticonvulsant medication. This association of dilantin with I.L. will undoubtedly be found more often in the future now that the characteristic features of i.L. are well described.2-4 The importance of remaining sweats.
Lukes, R: J., Tindle, B. H. New Engl. J. Med. 1975, 292, 1. Frizzera, G., Moran, E. M., Rappaport, H. Lancet, 1974, i, 1070. 3. Nomanbhoy, Y. T., Prager, P. R. ibid, 1974, ii, 409. 4. Horne, C. H. W., Fraser, R. A., Petric, J. C. ibid, p. 291.
1. 2.
of this association resides in the possibility of reversing I.L. by removal of the offending drug and starting chemotherapy early in the course of the lymphoproliferation. Until the cause and pathogenesis of I.L. are better understood, it will be important to continue reporting all drugs and antigens found associated with this disorder. aware
Department of Hematology-Oncology, Pathology, Chester, Pennsylvania, 19013, U.S.A.
MELVYN J. LAPES RAYMOND J. VIVACQUA KRISTINA ANTONIADES
CHROMOSOME ABNORMALITIES IN ANGIOIMMUNOBLASTIC LYMPHADENOPATHY SIR,-Angioimmunoblastic lymphadenopathy (A.LL.) has only lately become recognised as a distinct clinical and histological entity.’-3 Histologically the process is thought to be benign. However, Lukes and Tindle2 pointed to its potential transformation into malignant immunoblastic sarcoma. We studied the chromosome constitution of lymph-node-derived cells of 2 patients with this disease and found considerable anomalies in both cases. Case 1.- This 32-year-old man was found to have right cervical lymphadenopathy in April, 1975. In July, 1975, he presented with generalised lymphadenopathy, hepatosplenomegaly, fever (38.5-39.5"C), skin rash, eosinophilia (13%), and hypergammaglobulinaemia (immunoglobulins 5.33 g/dl, with an increase of IgM, IgG, and IgA). Lymph-node histology in July revealed non-specific lymphadenitis, but in August and November changes compatible with A.I.L. were seen. Chromosome analysis of 89 metaphases of lymph-nodederived cells in November, 1975, showed 19 hyperdiploid and 3 pseudodiploid. 11of the hyperdiploid metaphases had the karyotype 47, XY, +3. 2 others were 47, XY, +3, -9, +21 and 48, XY, +3, +8, +9, - 20, respectively. 5 other metaphases with 47 chromosomes, 1 with 49 chromosomes, and the pseudodiploid metaphases lacked a consistent pattern. Except for a brief period of prednisone therapy in June, 1975, the patient has had no treatment so far. CASE2.—A.I.L. was diagnosed in this 45-year-old man in September, 1974. Generalised lymphadenopathy developed in July, 1974, and on admission he was found to have hepatosplenomegaly, fever (38°C), a
history of weight-loss
and skin
allergy against
various substances,
eosinophilia (9%), and hyperglobulinmniia (immunoglobulins 1.6 edl, with an increase in M, G, and A components). Lymph-node histology in September and December, 1974, and March, 1975, indicated A.I.L. The chromosome constitution of lymph-node cells (direct preparation) was analysed in September and December, 1974, and the results, being almost identical, were pooled. Of 75 metaphases studied, 50 were hyperdiploid and 11 pseudodiploid. 8 of the pseudodiploid metaphases had a Bq+. 35 of the hyperdiploid metaphases had the karyotype 47,XY,Bq+,+lC, and 15 were 47,XY,+1C. No chromosome banding could be achieved. The chromosome constitution of phytohaemagglutinin-stimulated peripheral-blood lymphocytes was normal. At the time of lymph-node biopsies the patient was untreated. Since April, 1975, he has required prednisone therapy.
These are the only 2 patients with A.I.L. so far seen in our clinic. Both patients had chromosomally abnormal clones in the lymphatic tissue. Clones of cells carrying acquired chromosomal anomalies almost always indicate malignant growth, and our findings therefore cast some doubt on the notion that A.I.L. is a benign disease. They support the view of Lukes and Tindle2 that A.I.L. may be a "prelymphoma". Longitudinal studies will be necessary to determine whether or not all patients with A.I.L. have chromosome anomalies and whether those with anomalies are more likely to develop truly malignant
lymphomas.
D. K. H. is
supported by the Deutsche Forschungsgemeinschaft.
Medical University Clinic
(Tumour Research), Hufelandstrasse 55, 43 Essen 1.
D. K. HOSSFELD K. HÖFFKEN C. G. SCHMIDT
Josef Hospital, Mülheimerstrasse 83, 42 Oberhausen, Germany.
H. DIEDRICHS
1. Frizzera, G., Moran, E. M., Rappaport, H. Lancet, 1974, i, 1070. 2. Lukes, R. J., Tindle, B. H. New Engl. J. Med. 1975, 292,1. 3. Radaszkiewicz, T., Lennert, K. Dt. med. Wschr. 1975, 100, 1157.
St Bernard’s
Renal Unit,
Hospital,
Southall,
M. M. GLATT
Middlesex.
CIRRHOTIC GLOMERULONEPHRITIS AND SECRETORY IMMUNOGLOBULIN A
SiR,—Hyperglobulinxmia is a well-established feature of alcoholic liver cirrhosis, but the origin and the nature of this increased immune response is unknown. Callard et a1.3 found glomerular lesions in nine out of ten cirrhotic patients they investigated. The glomerulonephritis was characterised by the presence in the glomerulus of IgA, often associated with other immunoglobulins and C3. We have investigated twenty-two patients with proven alcoholic cirrhosis and compared them with twelve healthy subjects. Proteinuria was present in six patients with liver cirrhosis. Using discontinuous sucrose-gradient ultracentrifugation and reduction-alkylation of the immunoglobulins, we were able to measure serum monomeric and dimeric IgA levels along with IgM, IgG, and IgA-bound secretory component. By comparison with the controls, the cirrhotic patients presented the following increases of immunoglobulin concentrations: dimeric IgA 7.28 fold, monomeric IgA 2 41 fold, IgM 1.84 fold, IgG 1.56 fold, and IgA-bound secretory component 6.0 fold. As IgA and IgA-bound secretory component increased the most, we suggest that either IgA itself, originating from the gut, or its complex with bacterial, viral or dietary antigens, is deposited in the kidney and induces renal failure. IgA glomerular deposits in some cases of primary glomerulonephritis4 also probably have a mucosal, respiratory, or digestive, origin. Unite de Recherches de Physiopathologie
Digestive, INSERM U 45, Hôpital Edouard Herriot, Pavilion H,
A 42-year-old woman was referred for assessment of hypertension which had developed during her fourth pregnancy. Immediately after delivery the blood-pressure was 200/130 mm Hg lying and 160/120 mm Hg standing. At the same time creatinine clearance was 40 ml/min but rose after 2 weeks to 80 ml/min and has remained stable. An intravenous pyelogram and ultrasound evaluation were compatible with right-sided multicystic disease. The left kidney was elongated, with a duplex collecting system, but otherwise normal. Serum-IgA was undetectable. Blood-pressure was reduced to 150/90 mm Hg lying and standing with guanethidine 100 mg, clonidine 0-3mg, and spironolactone 50 mg daily. There was no past history of sinopulmonary infections, atopy, or use of the contraceptive pill. During follow-up for 20 months serum-IgA has remained undetectable, and the renal impairment has been stable. I wonder if the combination of hypertension, multicystic renal disease, and IgA deficiency is fortuitous or represents a genetic defect in this woman. I would be interested to learn of other cases.
FRANÇOISE ANDRÉ CLAUDE ANDRÉ
69374 Lyon, France.
IgA DEFICIENCY, HYPERTENSION, AND MULTICYSTIC RENAL DISEASE
Royal Infirmary,
ROGER GABRIEL
Hull.
ULTRASOUND AND SAFETY
(Oct. 18, p. 770) that the used in connection with the effect of ultra"mutagenic" sound on purified D.N.A. (Oct. 4, p. 662), is inappropriate, but we are not convinced by Dr Thacker’s other criticisms of our work. He argues that we have ignored evidence that does not support our recommendation to minimise ultrasound exposure of fetus. He maintains that degradation arises from hydrodynamic shear forces set up around oscillating or collapsing gas bubbles, but goes on to say that "to generate comparable shear forces in tissue a higher intensity would be required than that which degrades D.N.A. in solution, and were these forces sufficient to disrupt D.N.A. in chromosomes it is likely that damage to other cellular structures will be extensive enough to cause cell disruption and death." Hill’has pointed out that cavitation would happen in the liquid state but probably not in organised tissues, so we tried to work in conditions-frequencies of 2MHz and 0-87 MHz, volume of 7 ml, ambient pressure 1 bar, temperature below 25°C--below the cavitation threshold.3 The mechanism involved in the D.N.A. breaks we have observed is thus not clear. Hill has suggested that ultrasound could produce biological responses directly. The repeated vibrations, transmitted to the long, thin D.N.A. molecules, might produce shearing, and this mechanism might occur in vivo where cavitation is supposed not to happen. We have discussed these points elsewhere,4 taking into account Dr Thacker’s own review.5 We doubt whether cell disruption and death will necessarily happen before D.N.A. shearing. D.N.A., being the longest molecule in living cells, is therefore the most sensitive to shearing. Besides chromosome breaks happen at higher ultrasound intensities (in the W/cm2 range) :6-8 D.N.A. is sheared yet the cells are not dead. The presence of chromosome breaks rather than chromatid breaks means that the cells were sonicated at G,, and later went on to cell division. In our experiments we found that the intensities and durations necessary to break purified D.N.A. were uncomfortSm,—We
agree with Dr Thacker
term
SIR,-Your leading article
on selective IgA deficiency-’ report a patient with hypertension, multicystic renal disease, and absent serum-IgA, but with normal concentrations of IgM and IgG.
prompts me
to
1. Hill, C. R. J. acoust. Soc. Amr. 1972, 52. 667. 2. Hill, C. R. in Ultrasound in Clinical Diagnosis (edited by P. N. T. Wells); p. 165. Edinburgh, 1972. 3. Iernetti, G. Acustica, 1971, 24, 191. 4. Galperin-Lemaître, H., Kirsch-Volders, M., Levi, S. Humangenetik, 1975,
29, 61. 2 Glatt, M M. Lancet, 1975, i, 219. 3 Callard, P., Feldmann, G., Prandi, D., Belair, M. F., Mandet, C., Weiss, Y., Druet, P., Benhamou, J. P., Bariety, J. Am. J. Path. 1975, 80, 329. 4 Berger, J. Transplant Proc. 1969, 1, 939. 5 Lancet, 1975, ii, 1291.
5. Thacker, J. Curr. Topics Rad. Res. 1973, 8, 235. 6. Fischman, H. K., Coleman, D. J., Lizzi, F. L. J. Cell Biol. 1972, 55, 74a. 7. Slotova, J., Karpfel, Z., Hrazdira, I. Biol. Plant. 1967, 9, 49. 8. Coakley, W. T., Hugues, D. E., Slade, J. S., Laurence, K. M. Br. med. J. 1971, ii, 501.
198
ably close to the doses used in medical practice. As long as we remain ignorant of possible in-vivo effect on D.N.A. of ultrasound at medical doses, care should be taken when using sonication medicine, and uncontrolled peaks of high intensity should be avoided. Medical Genetics, Free University of Brussels, Faculty of Medicine, 97 rue aux Laines, 1000 Brussels, Belgium.
H. GALPERIN-LEMAITRE
Gynaecology and Obstetric Clinic, Brugmann University Hospital, Brussels.
S. LEVI
Crozer-Chester Medical Center,
IMMUNOBLASTIC LYMPHADENOPATHY ASSOCIATED WITH PHENYTOIN
(DIPHENYLHYDANTOIN) SIR,-Lukes and Tindle1 noted a frequent association of im-
lymphadenopathy (I.L.) with drug treatment, incase, diphenylhydantoin (’Dilantin’). Since there is a possibility that this lymphoproliferative process may be induced by chronic antigenic or drug stimulation, recognition of potentially provocative agents is important. We, too, have seen a patient who developed 1.L. while taking dilantin. A 78-year-old Black woman complained of fatigue and night
munoblastic
cluding,
in
one
She had arteriosclerotic cardiovascular disease and a seizure disorder requiring dilantin anticonvulsant therapy. Massive diffuse lymphadenopathy and hepatosplenomegaly were prominent physical findings. Her condition deteriorated rapidly over several weeks, despite stopping dilantin. Laboratory investigations showed: haemoglobin 10 g/dl; white blood-cell count 15 850 per mm3, with a predominance of reactive lymphocytes, plasmacytoid lymphocytes, and immunoblastic cells; platelet-count 72 000 per mm3; uric-acid 22 mg/dl; serum-protein electrophoresis 9.4 g/dl gammaglobulin, with a broad-based biclonal peak; quantitative immunoglobulin analysis showing two monoclonal proteins of kappa IgG’ and kappa IgA type (protein analysis performed by Dr Bias Frangione); direct Coombs test weakly positive; cryoglobulins and cryofibrinogen negative; Venereal Disease Research Laboratories and fluorescent-treponemal-antibody tests positive ; heterophile antibodies 1/28; positive rheumatoid factor; cold agglutinins 1/128. Lymph-node biopsy showed the angioimmunoblastic proliferation characteristic of i.L. Our diagnosis and slides were kindly reviewed and confirmed by Dr Henry Rappaport. Bonemarrow revealed lymphoproliferation consistent with i.L. This rapidly progressing and disabling disease was not influenced by discontinuing dilantin for 2 weeks, but physical findings and results of laboratory tests began to improve a few days after starting chemotherapy (cyclophosphamide, vincristine, prednisone) and were nearly normal after 2 months of observation and treatment. Prophylactic penicillin was also given because of serological evidence of syphilis. The patient died unexpectedly, apparently of her cerebrovascular disease, 2 months after starting treatment and 1 month after obtaining a clinical remission of her 1.L. At necropsy, I.L. was not apparent on external examination but was manifested by prominent lymph-node involvement, with abundant fibrosis and interstitial eosinophilic material, depletion of normal cells, and proliferation of vessels and plasmacytoid cells. Bone-marrow and spleen contained minor changes possibly related to 1.L. Cause of death was not established but was most likely related to her severe cardiovascular disease. No evidence of syphilis was found. This case illustrates’ the clinicopathological features of !.L. in a patient taking dilantin anticonvulsant medication. This association of dilantin with I.L. will undoubtedly be found more often in the future now that the characteristic features of i.L. are well described.2-4 The importance of remaining sweats.
Lukes, R: J., Tindle, B. H. New Engl. J. Med. 1975, 292, 1. Frizzera, G., Moran, E. M., Rappaport, H. Lancet, 1974, i, 1070. 3. Nomanbhoy, Y. T., Prager, P. R. ibid, 1974, ii, 409. 4. Horne, C. H. W., Fraser, R. A., Petric, J. C. ibid, p. 291.
1. 2.
of this association resides in the possibility of reversing I.L. by removal of the offending drug and starting chemotherapy early in the course of the lymphoproliferation. Until the cause and pathogenesis of I.L. are better understood, it will be important to continue reporting all drugs and antigens found associated with this disorder. aware
Department of Hematology-Oncology, Pathology, Chester, Pennsylvania, 19013, U.S.A.
MELVYN J. LAPES RAYMOND J. VIVACQUA KRISTINA ANTONIADES
CHROMOSOME ABNORMALITIES IN ANGIOIMMUNOBLASTIC LYMPHADENOPATHY SIR,-Angioimmunoblastic lymphadenopathy (A.LL.) has only lately become recognised as a distinct clinical and histological entity.’-3 Histologically the process is thought to be benign. However, Lukes and Tindle2 pointed to its potential transformation into malignant immunoblastic sarcoma. We studied the chromosome constitution of lymph-node-derived cells of 2 patients with this disease and found considerable anomalies in both cases. Case 1.- This 32-year-old man was found to have right cervical lymphadenopathy in April, 1975. In July, 1975, he presented with generalised lymphadenopathy, hepatosplenomegaly, fever (38.5-39.5"C), skin rash, eosinophilia (13%), and hypergammaglobulinaemia (immunoglobulins 5.33 g/dl, with an increase of IgM, IgG, and IgA). Lymph-node histology in July revealed non-specific lymphadenitis, but in August and November changes compatible with A.I.L. were seen. Chromosome analysis of 89 metaphases of lymph-nodederived cells in November, 1975, showed 19 hyperdiploid and 3 pseudodiploid. 11of the hyperdiploid metaphases had the karyotype 47, XY, +3. 2 others were 47, XY, +3, -9, +21 and 48, XY, +3, +8, +9, - 20, respectively. 5 other metaphases with 47 chromosomes, 1 with 49 chromosomes, and the pseudodiploid metaphases lacked a consistent pattern. Except for a brief period of prednisone therapy in June, 1975, the patient has had no treatment so far. CASE2.—A.I.L. was diagnosed in this 45-year-old man in September, 1974. Generalised lymphadenopathy developed in July, 1974, and on admission he was found to have hepatosplenomegaly, fever (38°C), a
history of weight-loss
and skin
allergy against
various substances,
eosinophilia (9%), and hyperglobulinmniia (immunoglobulins 1.6 edl, with an increase in M, G, and A components). Lymph-node histology in September and December, 1974, and March, 1975, indicated A.I.L. The chromosome constitution of lymph-node cells (direct preparation) was analysed in September and December, 1974, and the results, being almost identical, were pooled. Of 75 metaphases studied, 50 were hyperdiploid and 11 pseudodiploid. 8 of the pseudodiploid metaphases had a Bq+. 35 of the hyperdiploid metaphases had the karyotype 47,XY,Bq+,+lC, and 15 were 47,XY,+1C. No chromosome banding could be achieved. The chromosome constitution of phytohaemagglutinin-stimulated peripheral-blood lymphocytes was normal. At the time of lymph-node biopsies the patient was untreated. Since April, 1975, he has required prednisone therapy.
These are the only 2 patients with A.I.L. so far seen in our clinic. Both patients had chromosomally abnormal clones in the lymphatic tissue. Clones of cells carrying acquired chromosomal anomalies almost always indicate malignant growth, and our findings therefore cast some doubt on the notion that A.I.L. is a benign disease. They support the view of Lukes and Tindle2 that A.I.L. may be a "prelymphoma". Longitudinal studies will be necessary to determine whether or not all patients with A.I.L. have chromosome anomalies and whether those with anomalies are more likely to develop truly malignant
lymphomas.
D. K. H. is
supported by the Deutsche Forschungsgemeinschaft.
Medical University Clinic
(Tumour Research), Hufelandstrasse 55, 43 Essen 1.
D. K. HOSSFELD K. HÖFFKEN C. G. SCHMIDT
Josef Hospital, Mülheimerstrasse 83, 42 Oberhausen, Germany.
H. DIEDRICHS
1. Frizzera, G., Moran, E. M., Rappaport, H. Lancet, 1974, i, 1070. 2. Lukes, R. J., Tindle, B. H. New Engl. J. Med. 1975, 292,1. 3. Radaszkiewicz, T., Lennert, K. Dt. med. Wschr. 1975, 100, 1157.
