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Crystalline glomerular deposits in multiple myeloma
Crystalline
Glomerular
Multiple
in
Myeloma”
A
in protein metabolism, with crystalline deposits in widespread locations, have been described in “reticuloendothelioses,” and in multiple myeloma particularly. To our knowledge, review of some twenty-four cases has failed to disclose a case in which such deposits have been demonstrated in the glomeruli of the kidney. LGhlein [I] in 1921 reported a case in which protein crystals were demonstrated in kidney tubules. The author cited this case as the first in which such a demonstration was made. Microscopic examination of kidney sections revealed masses of crystals in dilated tubules of the cortex, and crystal-like exudates in the medullary tubules. The glomeruli were not affected. In a case of hemorrhagic purpura, huge cells containing a crystalline-like material were interpreted by Agress and Smith [Z] as being cells of the reticuloendothelial system. Crystalline deposits were demonstrated in the tubules of the kidney, with an accompanying inflammatory reaction; however, the glomeruli were not involved in these crystalline deposits. Brass [3], in a comprehensive study of twelve cases of “plasmacytoma,” found generalized crystalline deposits in various organs of the body, but made no mention of glomerular involvement. This same author in 1943 [d] reported a case of myeloma in which Bence Jones protein was demonstrated in the urine. The patient died in uremia, and microscopy of the kidney sections showed protein crystals which were recognized as Bence Jones protein precipitates. Again no glomerular involvement was noted. Severe kidney changes were reported by Miicke [5] in 1943. Six cases were reviewed, and in two myeloma was responsible for the alteration in protein metabolism. Two other
patients were syphilitics, one had “leukemic lymphadenosis” and achylia gastrica; in the sixth case no definite cause could be found. In three of the cases there were crystals within the kidney tubules; in two, tubules and interstitial tissue were involved; and in one case the crystals were intracellular in the epithelium of the tubules. Histologic examination showed an intact glomerular apparatus in these cases. Other patients with protein crystalline deposits in the renal tubules have been described by Neumann [6] and by Sikl[7] in 1949. The former also reported crystals in Bowman’s capsule. No glomerular involvement was noted. Multiple myeloma with the Fanconi syndrome and rodshaped inclusions within the tubular epithelium has been reported by Engle and Wallis [Z]. The glomeruli in this case were normal, except for a few which were sclerotic.
BERRATIONS
* From the Department of Pathology,
Deposits
CASE
REPORT
A sixty-five year old Negro man (No. C-375) entered the Chester Hospital on January 14, 1956, complaining of cough and chest pain of one week’s duration. Two weeks prior to admission he had had a chest cold which had become steadily worse. The patient denied having kidney disease, rheumatic disease, diabetes, tuberculosis or malignancy. There was no history of weight loss, dysuria or oliguria. Examination revealed an elderly Negro whose skin was moist and warm. Respiration was not labored. The blood pressure was 170/108 mm. Hg; pulse, 102; respirations, 24 per minute. There was some limitation of chest expansion on the left side. A localized enlargement, 3 to 4 cm. in diameter, was noted over the tenth rib posteriorly. Breath sounds were decreased over the left base, and vocal fremitus was increased. Dullness was present on percussion over the left base. The heart rhythm was regular, at a rate of 102 per minute. There were no murmurs. Chester Hospital, 354
Chester, Pennsylvania. AMERICAN
JOURNAL
OF
MEDlClNE
Ckystalline
Glomerular
Deposits in Myeloma-S&Ad
FIG. 1. Photomicrograph showing glomerulus and surrounding demonstrating Bence Jones protein crystals in the glomerulus.
Moderate cardiomegaly was noted on auscultation. The diagnosis on admission was pneumonitis, left base. Roentgenograms of the chest and abdomen taken on admission revealed an enlarged heart, and a possible lesion in the upper left abdominal quadrant. The urine gave an acid reaction, with a specific gravity of 1.009. A trace of proteinuria was noted. Many polymorphonuclear leukocytes, and 1 to 3 red blood cells per high power field were found. The hemoglobin was 8 gm. per cent with a hematocrit of 27 per cent. The leukocytes numbered 6,500 per cu. mm. with 22 per cent band cells, 44 per cent segmented forms, and 29 per cent lymphocytes. Eosinophils numbered 1 per cent and there were 4 per cent metamyelocytes. The blood urea nitrogen was reported on the second hospital day as 170 mg. per cent; serum calcium, 11.9 mg. per cent; plasma carbon dioxide, 10.2 mEq. per L.; chlorides, 104 mEq. per L.; potassium, 7.7 mEq. per L. and sodium, 148 mEq. per L. The hospital course was marked by severe oliguria (400 ml. per twenty-four hours), and on January 16 twitching appeared on the left side. The patient was “toxic” and drowsy. The blood pressure was 180/100 mm. Hg. The urine became bloody. The patient began to bleed from the nostrils. On January 17 a repeat electrolyte pattern showed a sodium of 132 mEq. per L., potassium, over 8 mEq. per L; chlorides, 98.2 mEq. per L. The plasma carbon dioxide had fallen to 8.4 mEq. per L. and the urea nitrogen was now 193 mg. per cent. In spite of fluid therapy and other supportive measures coma deepened. Convulsive seizures began, and the patient soon died. At autopsy (performed by Dr. Walter Levy) the body was that of a fairly well nourished Negro man. AUGUST,
1959
tissue.
355
and
Examination of the cardiovascular system revealed a heart weighing 350 gm. There was slight hypertrophy of the left ventricular wall, and the coronaries showed slight sclerosis. The valves, papillary muscles and chordae tendinae were essentially normal. The lungs were bluish gray, soft and doughy in consistency but extremely moist. Some emphysema was noted. No true consolidation was present. The liver presented a picture of chronic passive congestion. The pancreas, gallbladder and gastrointestinal tract were within normal limits, as were the spleen and adrenals. The grossly similar kidneys were enlarged and bulging, weighing 396 gm. each. Their external surfaces were finely granular, whitish gray with small focal areas of reddish tan color. Section of the kidneys revealed cortical zones which were enlarged to 1.3 cm. in thickness. They were mottled gray, and firm and tough in consistency. The entire cut surface of both organs presented innumerable white, pinpoint-sized dots, and were grossly suggestive of abscesses. Histologic examination of the kidneys revealed many parts of the nephrons to contain crystalloids of what appeared to be Bence Jones protein. Some crystalloids were needle-shaped, others were rhomboid. They were arranged singly, and in large aggregates. The distal tubules were involved, as were some of the proximal tubules. Many of the glomeruli showed dense crystalline deposits, which in some instances had all but obliterated the glomerular architecture. (Fig. 1.) Other glomeruli contained a minimal number of these crystals. These deposits had evoked a multinucleated foreign body reaction. Many multinucleated giant cells were noted, and around the
Crystalline
356
Glomerular
Deposits in Myeloma--&Ad
glomeruli were many polymorphonuclear leukocytes, lymphocytes and plasma cells. Where the deposits were lighter there appeared to be an early inflammatory infiltrate, without giant cells. The interstitium showed an increased fibrous tissue component. A benign arteriolar nephrosclerosis was present. Microscopic examination of the spleen revealed a dense plasmacytic infiltration. The lymph nodes showed extramedullary hematopoiesis. A bone marrow examination was not made.
SUMMARY
A case of multiple myeloma, unsuspected before autopsy, with crystalline deposits in the renal glomeruli is reported. It is postulated that these glomerular deposits were the chief cause of the renal failure, with oliguria, uremia and ultimate death. A brief review of the literature did not disclose previous mention of such crystalline deposits in the glomerular apparatus. REFERENCES
COMMENTS
The diagnosis of multiple myeloma in this patient was unsuspected until the autopsy was performed. This diagnosis was suggested by Dr. Arthur C. Allen [9], to whom the kidney sections were sent for study and an opinion. Following receipt of his suggestion an antemortem blood serum sample was studied by electrophoresis through the courtesy of Dr. Robert Norris, the University of Pennsylvania. The results of this study follow:
.
Albumin. Alpha) globulin. Alpha2 globulin. Beta globulin. Gamma globulin. Total protein(biuret).
This electrophoretic suggested multiple able before death.
2.5 0.77 1 .33 0.95 5.76 11 .3
gm. gm. gm. gm. gm. gm.
% % % % % %
(normal (normal (normal (normal (normal
3.5-4.7) 0.164.44 0.32-0.76 0.45-0.93 0.97-1.73
gm. gm. gm. gm.
%) W) %) %,)
curve certainly would have myeloma had it been avail-
1. L~~HLEIN,M. Eiweisskrystalle in den HarnkanSlchen bei multiplem My&m. Be&. P. Path. Amt. u. t. Allg. Path., 69: 295, 1921. 2. AGRESS,H. and SMITH, M. G. Purpura hemorrhagica
associated with widespread deposits of crystalline material; reticuloendotheliosis. Arch. Path., 29: 553,
1940. Die Eiweisstoffwechselstiirungen 3. BRASS, K. des Plasmacytomkranken. Frankfurt. Ztschr. Path., 57: 367, 1943. Die Eiweisstoffwechselstijrungen des 4. BRASS, K. qlasmacytomkranken. (II. Mitteilung.) Frankfurt. Ztschr. Pa+, 58: 56, 1943. 5. M~~cKE, P. Uber Ablagerungen van Eiweisskrystallen in der Niere. Frankfurt. Ztschr. Path., 58: 116, 1943. 6. NEUMANN, V. Multiple plasma cell myeloma with crystalline deposits in the tumor cells and in the kidneys. J. Path. & Bact., 61: 165, 1949. 7. SIKL, H. A case of diffuse plasmacytosis with deposition of protein crystals in the kidneys. J. Path. C3 Bat., 61: 149, 1949. 8. ENGLE, R. L. and WALLIS, L. A. Multiple myeloma and the adult Fanconi syndrome. Am. J. Med., 22: 5, 1957. 9. ALLEN, A. C. Personal communication.
AMERICAN
JOURNAL
OP
MEDICINE
Glomerular
Multiple
in
Myeloma”
A
in protein metabolism, with crystalline deposits in widespread locations, have been described in “reticuloendothelioses,” and in multiple myeloma particularly. To our knowledge, review of some twenty-four cases has failed to disclose a case in which such deposits have been demonstrated in the glomeruli of the kidney. LGhlein [I] in 1921 reported a case in which protein crystals were demonstrated in kidney tubules. The author cited this case as the first in which such a demonstration was made. Microscopic examination of kidney sections revealed masses of crystals in dilated tubules of the cortex, and crystal-like exudates in the medullary tubules. The glomeruli were not affected. In a case of hemorrhagic purpura, huge cells containing a crystalline-like material were interpreted by Agress and Smith [Z] as being cells of the reticuloendothelial system. Crystalline deposits were demonstrated in the tubules of the kidney, with an accompanying inflammatory reaction; however, the glomeruli were not involved in these crystalline deposits. Brass [3], in a comprehensive study of twelve cases of “plasmacytoma,” found generalized crystalline deposits in various organs of the body, but made no mention of glomerular involvement. This same author in 1943 [d] reported a case of myeloma in which Bence Jones protein was demonstrated in the urine. The patient died in uremia, and microscopy of the kidney sections showed protein crystals which were recognized as Bence Jones protein precipitates. Again no glomerular involvement was noted. Severe kidney changes were reported by Miicke [5] in 1943. Six cases were reviewed, and in two myeloma was responsible for the alteration in protein metabolism. Two other
patients were syphilitics, one had “leukemic lymphadenosis” and achylia gastrica; in the sixth case no definite cause could be found. In three of the cases there were crystals within the kidney tubules; in two, tubules and interstitial tissue were involved; and in one case the crystals were intracellular in the epithelium of the tubules. Histologic examination showed an intact glomerular apparatus in these cases. Other patients with protein crystalline deposits in the renal tubules have been described by Neumann [6] and by Sikl[7] in 1949. The former also reported crystals in Bowman’s capsule. No glomerular involvement was noted. Multiple myeloma with the Fanconi syndrome and rodshaped inclusions within the tubular epithelium has been reported by Engle and Wallis [Z]. The glomeruli in this case were normal, except for a few which were sclerotic.
BERRATIONS
* From the Department of Pathology,
Deposits
CASE
REPORT
A sixty-five year old Negro man (No. C-375) entered the Chester Hospital on January 14, 1956, complaining of cough and chest pain of one week’s duration. Two weeks prior to admission he had had a chest cold which had become steadily worse. The patient denied having kidney disease, rheumatic disease, diabetes, tuberculosis or malignancy. There was no history of weight loss, dysuria or oliguria. Examination revealed an elderly Negro whose skin was moist and warm. Respiration was not labored. The blood pressure was 170/108 mm. Hg; pulse, 102; respirations, 24 per minute. There was some limitation of chest expansion on the left side. A localized enlargement, 3 to 4 cm. in diameter, was noted over the tenth rib posteriorly. Breath sounds were decreased over the left base, and vocal fremitus was increased. Dullness was present on percussion over the left base. The heart rhythm was regular, at a rate of 102 per minute. There were no murmurs. Chester Hospital, 354
Chester, Pennsylvania. AMERICAN
JOURNAL
OF
MEDlClNE
Ckystalline
Glomerular
Deposits in Myeloma-S&Ad
FIG. 1. Photomicrograph showing glomerulus and surrounding demonstrating Bence Jones protein crystals in the glomerulus.
Moderate cardiomegaly was noted on auscultation. The diagnosis on admission was pneumonitis, left base. Roentgenograms of the chest and abdomen taken on admission revealed an enlarged heart, and a possible lesion in the upper left abdominal quadrant. The urine gave an acid reaction, with a specific gravity of 1.009. A trace of proteinuria was noted. Many polymorphonuclear leukocytes, and 1 to 3 red blood cells per high power field were found. The hemoglobin was 8 gm. per cent with a hematocrit of 27 per cent. The leukocytes numbered 6,500 per cu. mm. with 22 per cent band cells, 44 per cent segmented forms, and 29 per cent lymphocytes. Eosinophils numbered 1 per cent and there were 4 per cent metamyelocytes. The blood urea nitrogen was reported on the second hospital day as 170 mg. per cent; serum calcium, 11.9 mg. per cent; plasma carbon dioxide, 10.2 mEq. per L.; chlorides, 104 mEq. per L.; potassium, 7.7 mEq. per L. and sodium, 148 mEq. per L. The hospital course was marked by severe oliguria (400 ml. per twenty-four hours), and on January 16 twitching appeared on the left side. The patient was “toxic” and drowsy. The blood pressure was 180/100 mm. Hg. The urine became bloody. The patient began to bleed from the nostrils. On January 17 a repeat electrolyte pattern showed a sodium of 132 mEq. per L., potassium, over 8 mEq. per L; chlorides, 98.2 mEq. per L. The plasma carbon dioxide had fallen to 8.4 mEq. per L. and the urea nitrogen was now 193 mg. per cent. In spite of fluid therapy and other supportive measures coma deepened. Convulsive seizures began, and the patient soon died. At autopsy (performed by Dr. Walter Levy) the body was that of a fairly well nourished Negro man. AUGUST,
1959
tissue.
355
and
Examination of the cardiovascular system revealed a heart weighing 350 gm. There was slight hypertrophy of the left ventricular wall, and the coronaries showed slight sclerosis. The valves, papillary muscles and chordae tendinae were essentially normal. The lungs were bluish gray, soft and doughy in consistency but extremely moist. Some emphysema was noted. No true consolidation was present. The liver presented a picture of chronic passive congestion. The pancreas, gallbladder and gastrointestinal tract were within normal limits, as were the spleen and adrenals. The grossly similar kidneys were enlarged and bulging, weighing 396 gm. each. Their external surfaces were finely granular, whitish gray with small focal areas of reddish tan color. Section of the kidneys revealed cortical zones which were enlarged to 1.3 cm. in thickness. They were mottled gray, and firm and tough in consistency. The entire cut surface of both organs presented innumerable white, pinpoint-sized dots, and were grossly suggestive of abscesses. Histologic examination of the kidneys revealed many parts of the nephrons to contain crystalloids of what appeared to be Bence Jones protein. Some crystalloids were needle-shaped, others were rhomboid. They were arranged singly, and in large aggregates. The distal tubules were involved, as were some of the proximal tubules. Many of the glomeruli showed dense crystalline deposits, which in some instances had all but obliterated the glomerular architecture. (Fig. 1.) Other glomeruli contained a minimal number of these crystals. These deposits had evoked a multinucleated foreign body reaction. Many multinucleated giant cells were noted, and around the
Crystalline
356
Glomerular
Deposits in Myeloma--&Ad
glomeruli were many polymorphonuclear leukocytes, lymphocytes and plasma cells. Where the deposits were lighter there appeared to be an early inflammatory infiltrate, without giant cells. The interstitium showed an increased fibrous tissue component. A benign arteriolar nephrosclerosis was present. Microscopic examination of the spleen revealed a dense plasmacytic infiltration. The lymph nodes showed extramedullary hematopoiesis. A bone marrow examination was not made.
SUMMARY
A case of multiple myeloma, unsuspected before autopsy, with crystalline deposits in the renal glomeruli is reported. It is postulated that these glomerular deposits were the chief cause of the renal failure, with oliguria, uremia and ultimate death. A brief review of the literature did not disclose previous mention of such crystalline deposits in the glomerular apparatus. REFERENCES
COMMENTS
The diagnosis of multiple myeloma in this patient was unsuspected until the autopsy was performed. This diagnosis was suggested by Dr. Arthur C. Allen [9], to whom the kidney sections were sent for study and an opinion. Following receipt of his suggestion an antemortem blood serum sample was studied by electrophoresis through the courtesy of Dr. Robert Norris, the University of Pennsylvania. The results of this study follow:
.
Albumin. Alpha) globulin. Alpha2 globulin. Beta globulin. Gamma globulin. Total protein(biuret).
This electrophoretic suggested multiple able before death.
2.5 0.77 1 .33 0.95 5.76 11 .3
gm. gm. gm. gm. gm. gm.
% % % % % %
(normal (normal (normal (normal (normal
3.5-4.7) 0.164.44 0.32-0.76 0.45-0.93 0.97-1.73
gm. gm. gm. gm.
%) W) %) %,)
curve certainly would have myeloma had it been avail-
1. L~~HLEIN,M. Eiweisskrystalle in den HarnkanSlchen bei multiplem My&m. Be&. P. Path. Amt. u. t. Allg. Path., 69: 295, 1921. 2. AGRESS,H. and SMITH, M. G. Purpura hemorrhagica
associated with widespread deposits of crystalline material; reticuloendotheliosis. Arch. Path., 29: 553,
1940. Die Eiweisstoffwechselstiirungen 3. BRASS, K. des Plasmacytomkranken. Frankfurt. Ztschr. Path., 57: 367, 1943. Die Eiweisstoffwechselstijrungen des 4. BRASS, K. qlasmacytomkranken. (II. Mitteilung.) Frankfurt. Ztschr. Pa+, 58: 56, 1943. 5. M~~cKE, P. Uber Ablagerungen van Eiweisskrystallen in der Niere. Frankfurt. Ztschr. Path., 58: 116, 1943. 6. NEUMANN, V. Multiple plasma cell myeloma with crystalline deposits in the tumor cells and in the kidneys. J. Path. & Bact., 61: 165, 1949. 7. SIKL, H. A case of diffuse plasmacytosis with deposition of protein crystals in the kidneys. J. Path. C3 Bat., 61: 149, 1949. 8. ENGLE, R. L. and WALLIS, L. A. Multiple myeloma and the adult Fanconi syndrome. Am. J. Med., 22: 5, 1957. 9. ALLEN, A. C. Personal communication.
AMERICAN
JOURNAL
OP
MEDICINE