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The hepatopathy of hypernephroma
The Hepatopathy
of Hypernephroma
WILLIAM T. LEMMON, JR., M.D., PAUL V. HOLLAND, M.D., AND JAMES M. HOLLAND, M.D.,
Bethesda, Maryland
From the Surgery Branch of the Nationai Cancer Institute and the Clinical Center Blood Bank, National Institutes of Health, Bethesda, Maryland.
are notorious for such unusual clinical manifestations as anemia, polycythemia, fever, hypercalcemia, serum protein abnormalities, and secondary amyloidosis [l ,.?I. A review of 273 hypernephromas with atypical features does not mention hepatic dysfunction [I]. Infrequent references to the association of abnormal liver function tests with hypernephroma have appeared since 1961 [3-81. The unusual hypernephroma to be reported presented a laboratory picture of severe hepatic dysfunction which dominated the clinical course until the kidney and a rapidly growing solitary pulmonary metastasis were excised.
H
YPERNEPHROMAS
CASE REPORT A forty-five year old housewife was referred to the National Institutes of Health in October 1963, for evaluation of anemia and splenomegaly. Burning subxiphoid pain led to the roentgenographic diagnosis of duodenal ulcer five years previously. At that time she was rejected as a blood donor because of anemia. Progressive fatigue, unresponsive to parenteral hematinics, was manifest for three years before detection of an abdominal mass prompted hospitalization. The mass in the left upper quadrant extended 8 cm. below the costal margin. The liver was not enlarged. Hypochromic anemia, leukocytosis, and an elevated platelet count were noted. (Table I.) The direct Coombs’ test was negative and cold agglutinins and lupus erythematosus cells were not detected. The prothrombin time and bromsulphalein retention were abnormal. (Table II.) Needle biopsy of the liver was interpreted to be within normal limits although parenchymal cells contained moderate amounts of hemosiderin. Aspiration biopsy of the left upper quadrant mass demonstrated cells with “foamy cytoplasm resembling the fat-laden histiocytes of Niemann-Pick’s disease.” She was given two units of packed red blood cells. Vol. 110, September
1965
487
Three months later, on the first admission to the Clinical Center, the patient described a 2G pound (11.8 kg.) weight loss during the preceding two years, Night sweats, frequent fevers to 38.5’~., anorexia, and sharp left upper abdominal pain had been present for three months. Genitourinary symptoms were absent. Antacids, hematinics, and propoxyphene hydrochloride were the only medications administered to the patient. Alcohol ingestion was minimal and exposure to hepatotoxins denied. Physical examination revealed temperature elevation to 38’c., blood pressure 94 mm. Hg systolic, 64 mm. Hg diastolic, evident weight loss, pallor, and a visible, firm, tender abdominal mass. No liver enlargement was present. Hypochromic microcytic anemia (Table I) and abnormal values for serum alkaline phosphatase, protein electrophoresis, prothrombin time and bromsulphalein retention were noted. (Table II.) Proteinuria, pyuria, and hematuria were absent. An electrocardiogram, oral cholecystogram, and bone marrow biopsy were normal. Upper gastrointestinal roentgenograms demonstrated a large mass displacing the stomach (Fig. 1) and a deformed duodenal bulb without spasm or crater formation. The overpenetrated films for this study revealed a left lower lobe pulmonary mass. Serial tomograms (Fig. 2) demonstrated its subsequent growth. Intravenous pyelography revealed a large intrarenal mass distorting the left renal collecting system, confirmed by retrograde pyelography and left renal arteriography. (Fig. 3.) The inferior vena cavagram did not demonstrate extension of tumor into the vena cava. Lymphangiography was noncontributory. Abdominal exploration, left nephrectomy, and liver biopsy were performed transabdominally using sodium pentothal and nitrous oxide anesthesia. The liver was pale, soft, and free of gross tumor. Microscopically, moderate fatty changes and minimal parenchymal hemosiderin deposition were present, The spleen was normal in size and appearance. The kidney weighed 1,020 gm., and was almost totally replaced by clear cell carcinoma which also invaded the renal vein. Surgery was tolerated unusually well and the postoperative liver function tests showed temporary
* Isoeozyme
49 47
10/31/63 11/14/63 11/21/63 12/2/63 12j6/63 l/10/64 l/20/64 l/27/64 3/13/64 3/23/64 3/26/64 3/27/64 3/31/64 4/7/64 4/15/64 5/22/64 7/22/64 10/23/64
pattern
16 14 11 18 12 14 12
23 15 58 29* 25 13 10
36
determined
5.70 5.10 5.20
...
4.95 5.05 5.30 5.40
I
160
. .
M.D.
1.2/0.82 0.7/0.36 0.9/0.39 0.6/O. 18 0.1/0.5 0.2/0.07 0.2/o. 12
0.5/0.26 0.6/0.26 0. 1;o. 07 0.5/0.22
. .. .
. 0.4/O. 25
0.3/0.08
o.wo.3
(mg./lOO)
Bili/Dir.
by H. F. Taswell.
4.6 3.4 2.6
.
3.7 3.2 3.3
.
.
.
4.3
5.90
. .. ...
..
.
5.31
4.0
335 180
43 37 42 42
13.6 11.6 13.1 13.5
51.2 53.8 57.9 59.9
4.3
225 258 175 203
39 35 43 47
11.9 10.8 13.5 14.7
39.6 42.9 48.7 54.2
617 533
26 31 30 27
8.3 9.3 9.0 7.7
.
3
. .
.
26
28
34 23
4 6 5 2
6 5 6 3 2 5
.
..
.
... . .
N
+“+ +-J-c La&&mzy, . N
N
. . . . .
.
CCF
N
.
24 29
II
10 10
M
261 23 454 Left Lower 110 76 23 22 13 10 14
20 Nephrectomy . . 39 390 285
14
--.
309 23 985 Lobeclomy 340 204 34 49 10 14 30
::: 475 445
26
21
9
Cu.)
Cu.)
12
SGPT Ksrmen
SGOT Karmen
CHEMISTRIES
TABLE
. 15 15
I HEMATOLOGY
Nefihveclomy 59 32 8 66 26 3 53 38 7 55 33 8 Lafiarolomy, Lobecfomy 70 14 10 60 29 9 57 39 2 67 29 2
63 60
+ 3
AND
TABLE
_~Differential PMN L
CLINICAL
TT Shank Hoagland units
8.3 7.6 6.9 5.1
8.9 9.4 6.6 6.6
11.8 11.2 7.9 7.5
W.B.C. (10 -~/mm.a)
WEIGHT
11.5
(%) Ret’n.
BSP
0.5 0.1
.
1.0 0.7 0.5
.
0.7 0.8
(%)
46.4 45.3 44.6 43.6
Retie.
Plat.
(kg.)
(X 10 -a/mm.v
Hct. (%I
Hgb.
(gm./lOO)
Wgt.
10/24/63
7/63
Date
7/63 10/23/63 11/4/63 11/9/63 11/21/63 1 i/29/63 12/6/63 l/20/64 3/23/64 3/26/64 4/X/64 5/22/64 7/22/64 10/23/64
Date
BODY
6 2 2 1
1 4 2 4
3 1
I?
1,885 _.. 1.050 ’ 770 464 1,250 697 292 338 317
705
:::
Cu.)
LDH
93 23
14 32
a7
104
. 92
70 50 50 70
(%)
Pro. Time
ESR (mm./hr.)
89 90
‘si .‘.
4.3 4.3
3.8
3.7
2.4 2.7
1.8 1.9
P-IndicesMCV
0.3
0.8 0.7
Protein
31 32
...
30
MCHC
(gZ./100)
Serum
27 28
20’ “.
MCH
0.3
1.1 1.1
0.8
1.1
1.1
1.8
2.0 1.9
168
169
TIBC (rgm./lOO)
Electrophoresis----
24
19
FE (pgm./lOO)
Hepatopathy
-Ml
of Hypermephroma
regeneration although a moderate lymphocytic infiltration of the portal zones was present. Left lower lobectomp with en bloc resection of the parictal pleura removed the metastatic focus, which was identical histopathologically to the primary renal tumor. Rapid improvement in the liver function tests was evident before discharge. (Table II). Two months after surgery, no liver enlargement could be detected and the patient felt well. Seven months after lobectomy, the patient was entirely well, the chest and skeletal roentgenograms were normal, and all liver function tests had returned to normal values. (Table II.) ~4lkc~line Phasphatase Isoemymes. Using starch gel electrclphoresis, Taswell reported a fast alpha alkaline phosphatase isoenzyme in a hypernephroma patient with liver metastases [9]. His analysis of a January 1963 specimen from our patient did not demonstrate the fast alpha isoenzyme but did show elevated beta, the presence of alpha-l and beta lipoprotein, and a very faint origin alkaline phosphatase isoenzyme zone [IO]. This isoenzpme pattern was consistent with parenchymal liver disease [Y]. COMMENTS
The hepatopathy of hypernephroma is more than the few cases reported in the literature would indicate [3X?]. Similar cases with more complete testing of liver function [II-would have recognized this hepatopathy
common FIG. 1. Upper gastrointestinal series. The stomach is stretched across the large mass in the left upper quadrant. The small intestine is displaced inferiorly and to the right. improvement.
iTable II. ) Examination six weeks later revealed continued weight gain (Table I), a normal hemogram, and striking improvement in physical appearance. Icterus and hepatosplenomegaly were absent. The enlarging pulmonary metastasis and elevated alkaline phosphatase and transaminase levels belied the apparent excellent response. Radiographic skeletal survey disclosed no osseous lesions. Radiogold liver scan confirmed the absence of hepatomegaly but demonstrated several areas of decreased activity in the right lobe that were not characteristic of metastatic involvement. The patient continued her rapid weight gain and described no hepatic symptoms. The further growth of metastasis, causing the onset of pleuritic chest pain, prompted readmission two months later. A soft, smooth, rounded liver edge was now palpable 2 cm. below the costal margin. Skeletal survey and radiogold liver scan were normal. The laboratory pattern of hepatic dysfunction again revealed elevations of the transaminase and lactic dehydrogenase enzymes. (Table II.) Under cyclopropane anesthesia, preliminary laparotomy revealed a liver normal in color and consistency with no evidence of tumor either in the liver or at the nephrectomy site. Liver biopsy demonstrated no parenchymal inflammation, necrosis, or Vol.
110,
Seplembr~u
1965
131. The reported cases follow a similar pattern. Often they are diagnostic problems that have presented months of unexplained fever, progressive weight loss, fatigue, and anemia. Hepatosplenomegaly is sometimes present. Finally, the discovery of an abdominal mass or the appearance of hypercalcemia precipitates a complete laboratory investigation which exposes the hepatopathy. When the liver biopsy shows nonspecific changes, little further attention is paid the hepatic dysfunction because the patient does not symptomatically reflect the chemical abnormalities. The full laboratory picture reveals abnormal values for serum alkaline phosphatase, bromsulphalein retention, flocculation tests, prothrombin time, and serum protein electrophoresis. Later, a phase of transaminase and lactic dehydrogenase enzyme elevations may occur. Serial determinations of these tests demonstrate marked variation which is diagnostically more important than the magnitude of the abnormalities per se. The possibility that anicteric hepatitis, either serum or infectious, caused the hepatopathy observed is not supported by histopathologic examination of the serial liver biopsies ob-
Lemmon, Holland, and Holland
490
FIG. 2. Pulmonary tomography. Serial tomograms metastases over a five month period.
demonstrate
the rapid growth of the solitary pulmonary
FIG. 3. Intravenous pyelogram, retrograde pyelogram and renal arteriogram. The huge left renal mass, the distorted pelvocalyceal collecting system, and the vascular “tumor blush” demonstrate the characteristics of hypernephroma.
tamed. It is unlikely that laboratory abnormalities would immediately improve after anesthesia and surgery or that the observed rapid gains in appetite, weight, and strength would occur in the presence of hepatitis. Two other operable cases demonstrated complete remission of the hepatic dysfunction after removal of the tumor [3,7]. This unusual hepatopathy should not contraindicate the surgical removal of a hypernephroma that would otherwise appear curable, for widespread metastatic disease has not been reported in the cases observed. SUMMARY
AND
CONCLUSIONS
A hypernephroma simulating severe recurrent liver disease is reported and related cases from the literature reviewed. Abnormal values for alkaline phosphatase, prothrombin time,
flocculation tests, protein electrophoresis, bromsulphalein retention, and liver enzymes oxalacetic transaminase, (serum glutamic serum glutamic pyruvic transaminase, lactic dehydrogenase) were found which varied considerably during the course of the illness. No characteristic histopathologic picture was found despite serial liver biopsies. The abnormalvalues returned to normal after removal of the primary tumor and a solitary pulmonary metastasis. The hepatopathy should not be a contraindication to surgery and indeed may aid the diagnostician confronted with a masquerading hypernephroma. REFERENCES
1. BERGER, L. and SINKOFF, M. W. Systemic manifestations of hypernephroma. Am. J. Med., 22: 791, 1957. 2. PINALS, R. S. and KRANE, S. M. Medical aspects of American
Journal
of Surzery
Hepatopathy
of Hypernephroma
renal carcinoma. Postg~ad. 151.J., 38: 507, 1962. 3. Case records of the Massachusetts General Hospital (C!:tse SO-1961 ). Ne%l Eq$and J. Xed., 265: 953, 1961. 4. SHIPMAS, K. H., DOKNING, S. W., and BRADFORD, H. A. Hypernephroma presenting as fever of unknown origin associated with elevated sertml alkaline phosphatase levels. J. l’rol., 89: 160, 1963. 5. STAUFFER,M. H. I\;ephrogenic hepatosplenomegaly. (;nstrornl~roZopy, 40 : 694, 1961. 6. DAVID, S. ,T., VERNER, J. Y., and ENGEI,, F. L. The diagnostic spectrum of hypercalcemia. Am. J. Med., 33 : 88, 1962. 7. TREMRLAY, H. E. and ANSELL, J. S. Carcinoma of the kidney simulating hyperparathyroidism. J. l’rol., 91 : 10, 1964. 8. GOLDRERG. M. F., TASIIJIAX, A. H., JR., ORDER,
Vol. 110, Se~tenzbev
1965
9.
10 11
12.
13.
,491
S. E., and DADI&IIN,G. J. Renal adenocarcinoma containing a parathyroid hormone-like substance and associated with marked hypercalcrmia. .,lm. J. di’ed., 36: 805, 1964. TASXELL, H. F. and JEFFERS, D. M. Isoenzymes of serum alkaline phosphatase in hepatobiliary and skeletal diseast. :lnr. J. C/in. I-‘&h., 40: 319, 196::. TAS\VE:LL,H. F. Personal communication. PLI>IP.IY)P~,C. H. and GELLIIORN, .A. Hypercalccmia in malignant disease without evidence of bone destruction. An?. J. Med., 21: 750, 1956. Case records of the Massachusetts General Hospital (Case Y-1961), ,V~ZPI England J. died., 264: 242, 1961. PETERSDORF, K. G. and BEESOS, P. B. Fever of unexplained origin : report on 100 cases. :Vedic-Ae, 40:1, 1961.
of Hypernephroma
WILLIAM T. LEMMON, JR., M.D., PAUL V. HOLLAND, M.D., AND JAMES M. HOLLAND, M.D.,
Bethesda, Maryland
From the Surgery Branch of the Nationai Cancer Institute and the Clinical Center Blood Bank, National Institutes of Health, Bethesda, Maryland.
are notorious for such unusual clinical manifestations as anemia, polycythemia, fever, hypercalcemia, serum protein abnormalities, and secondary amyloidosis [l ,.?I. A review of 273 hypernephromas with atypical features does not mention hepatic dysfunction [I]. Infrequent references to the association of abnormal liver function tests with hypernephroma have appeared since 1961 [3-81. The unusual hypernephroma to be reported presented a laboratory picture of severe hepatic dysfunction which dominated the clinical course until the kidney and a rapidly growing solitary pulmonary metastasis were excised.
H
YPERNEPHROMAS
CASE REPORT A forty-five year old housewife was referred to the National Institutes of Health in October 1963, for evaluation of anemia and splenomegaly. Burning subxiphoid pain led to the roentgenographic diagnosis of duodenal ulcer five years previously. At that time she was rejected as a blood donor because of anemia. Progressive fatigue, unresponsive to parenteral hematinics, was manifest for three years before detection of an abdominal mass prompted hospitalization. The mass in the left upper quadrant extended 8 cm. below the costal margin. The liver was not enlarged. Hypochromic anemia, leukocytosis, and an elevated platelet count were noted. (Table I.) The direct Coombs’ test was negative and cold agglutinins and lupus erythematosus cells were not detected. The prothrombin time and bromsulphalein retention were abnormal. (Table II.) Needle biopsy of the liver was interpreted to be within normal limits although parenchymal cells contained moderate amounts of hemosiderin. Aspiration biopsy of the left upper quadrant mass demonstrated cells with “foamy cytoplasm resembling the fat-laden histiocytes of Niemann-Pick’s disease.” She was given two units of packed red blood cells. Vol. 110, September
1965
487
Three months later, on the first admission to the Clinical Center, the patient described a 2G pound (11.8 kg.) weight loss during the preceding two years, Night sweats, frequent fevers to 38.5’~., anorexia, and sharp left upper abdominal pain had been present for three months. Genitourinary symptoms were absent. Antacids, hematinics, and propoxyphene hydrochloride were the only medications administered to the patient. Alcohol ingestion was minimal and exposure to hepatotoxins denied. Physical examination revealed temperature elevation to 38’c., blood pressure 94 mm. Hg systolic, 64 mm. Hg diastolic, evident weight loss, pallor, and a visible, firm, tender abdominal mass. No liver enlargement was present. Hypochromic microcytic anemia (Table I) and abnormal values for serum alkaline phosphatase, protein electrophoresis, prothrombin time and bromsulphalein retention were noted. (Table II.) Proteinuria, pyuria, and hematuria were absent. An electrocardiogram, oral cholecystogram, and bone marrow biopsy were normal. Upper gastrointestinal roentgenograms demonstrated a large mass displacing the stomach (Fig. 1) and a deformed duodenal bulb without spasm or crater formation. The overpenetrated films for this study revealed a left lower lobe pulmonary mass. Serial tomograms (Fig. 2) demonstrated its subsequent growth. Intravenous pyelography revealed a large intrarenal mass distorting the left renal collecting system, confirmed by retrograde pyelography and left renal arteriography. (Fig. 3.) The inferior vena cavagram did not demonstrate extension of tumor into the vena cava. Lymphangiography was noncontributory. Abdominal exploration, left nephrectomy, and liver biopsy were performed transabdominally using sodium pentothal and nitrous oxide anesthesia. The liver was pale, soft, and free of gross tumor. Microscopically, moderate fatty changes and minimal parenchymal hemosiderin deposition were present, The spleen was normal in size and appearance. The kidney weighed 1,020 gm., and was almost totally replaced by clear cell carcinoma which also invaded the renal vein. Surgery was tolerated unusually well and the postoperative liver function tests showed temporary
* Isoeozyme
49 47
10/31/63 11/14/63 11/21/63 12/2/63 12j6/63 l/10/64 l/20/64 l/27/64 3/13/64 3/23/64 3/26/64 3/27/64 3/31/64 4/7/64 4/15/64 5/22/64 7/22/64 10/23/64
pattern
16 14 11 18 12 14 12
23 15 58 29* 25 13 10
36
determined
5.70 5.10 5.20
...
4.95 5.05 5.30 5.40
I
160
. .
M.D.
1.2/0.82 0.7/0.36 0.9/0.39 0.6/O. 18 0.1/0.5 0.2/0.07 0.2/o. 12
0.5/0.26 0.6/0.26 0. 1;o. 07 0.5/0.22
. .. .
. 0.4/O. 25
0.3/0.08
o.wo.3
(mg./lOO)
Bili/Dir.
by H. F. Taswell.
4.6 3.4 2.6
.
3.7 3.2 3.3
.
.
.
4.3
5.90
. .. ...
..
.
5.31
4.0
335 180
43 37 42 42
13.6 11.6 13.1 13.5
51.2 53.8 57.9 59.9
4.3
225 258 175 203
39 35 43 47
11.9 10.8 13.5 14.7
39.6 42.9 48.7 54.2
617 533
26 31 30 27
8.3 9.3 9.0 7.7
.
3
. .
.
26
28
34 23
4 6 5 2
6 5 6 3 2 5
.
..
.
... . .
N
+“+ +-J-c La&&mzy, . N
N
. . . . .
.
CCF
N
.
24 29
II
10 10
M
261 23 454 Left Lower 110 76 23 22 13 10 14
20 Nephrectomy . . 39 390 285
14
--.
309 23 985 Lobeclomy 340 204 34 49 10 14 30
::: 475 445
26
21
9
Cu.)
Cu.)
12
SGPT Ksrmen
SGOT Karmen
CHEMISTRIES
TABLE
. 15 15
I HEMATOLOGY
Nefihveclomy 59 32 8 66 26 3 53 38 7 55 33 8 Lafiarolomy, Lobecfomy 70 14 10 60 29 9 57 39 2 67 29 2
63 60
+ 3
AND
TABLE
_~Differential PMN L
CLINICAL
TT Shank Hoagland units
8.3 7.6 6.9 5.1
8.9 9.4 6.6 6.6
11.8 11.2 7.9 7.5
W.B.C. (10 -~/mm.a)
WEIGHT
11.5
(%) Ret’n.
BSP
0.5 0.1
.
1.0 0.7 0.5
.
0.7 0.8
(%)
46.4 45.3 44.6 43.6
Retie.
Plat.
(kg.)
(X 10 -a/mm.v
Hct. (%I
Hgb.
(gm./lOO)
Wgt.
10/24/63
7/63
Date
7/63 10/23/63 11/4/63 11/9/63 11/21/63 1 i/29/63 12/6/63 l/20/64 3/23/64 3/26/64 4/X/64 5/22/64 7/22/64 10/23/64
Date
BODY
6 2 2 1
1 4 2 4
3 1
I?
1,885 _.. 1.050 ’ 770 464 1,250 697 292 338 317
705
:::
Cu.)
LDH
93 23
14 32
a7
104
. 92
70 50 50 70
(%)
Pro. Time
ESR (mm./hr.)
89 90
‘si .‘.
4.3 4.3
3.8
3.7
2.4 2.7
1.8 1.9
P-IndicesMCV
0.3
0.8 0.7
Protein
31 32
...
30
MCHC
(gZ./100)
Serum
27 28
20’ “.
MCH
0.3
1.1 1.1
0.8
1.1
1.1
1.8
2.0 1.9
168
169
TIBC (rgm./lOO)
Electrophoresis----
24
19
FE (pgm./lOO)
Hepatopathy
-Ml
of Hypermephroma
regeneration although a moderate lymphocytic infiltration of the portal zones was present. Left lower lobectomp with en bloc resection of the parictal pleura removed the metastatic focus, which was identical histopathologically to the primary renal tumor. Rapid improvement in the liver function tests was evident before discharge. (Table II). Two months after surgery, no liver enlargement could be detected and the patient felt well. Seven months after lobectomy, the patient was entirely well, the chest and skeletal roentgenograms were normal, and all liver function tests had returned to normal values. (Table II.) ~4lkc~line Phasphatase Isoemymes. Using starch gel electrclphoresis, Taswell reported a fast alpha alkaline phosphatase isoenzyme in a hypernephroma patient with liver metastases [9]. His analysis of a January 1963 specimen from our patient did not demonstrate the fast alpha isoenzyme but did show elevated beta, the presence of alpha-l and beta lipoprotein, and a very faint origin alkaline phosphatase isoenzyme zone [IO]. This isoenzpme pattern was consistent with parenchymal liver disease [Y]. COMMENTS
The hepatopathy of hypernephroma is more than the few cases reported in the literature would indicate [3X?]. Similar cases with more complete testing of liver function [II-would have recognized this hepatopathy
common FIG. 1. Upper gastrointestinal series. The stomach is stretched across the large mass in the left upper quadrant. The small intestine is displaced inferiorly and to the right. improvement.
iTable II. ) Examination six weeks later revealed continued weight gain (Table I), a normal hemogram, and striking improvement in physical appearance. Icterus and hepatosplenomegaly were absent. The enlarging pulmonary metastasis and elevated alkaline phosphatase and transaminase levels belied the apparent excellent response. Radiographic skeletal survey disclosed no osseous lesions. Radiogold liver scan confirmed the absence of hepatomegaly but demonstrated several areas of decreased activity in the right lobe that were not characteristic of metastatic involvement. The patient continued her rapid weight gain and described no hepatic symptoms. The further growth of metastasis, causing the onset of pleuritic chest pain, prompted readmission two months later. A soft, smooth, rounded liver edge was now palpable 2 cm. below the costal margin. Skeletal survey and radiogold liver scan were normal. The laboratory pattern of hepatic dysfunction again revealed elevations of the transaminase and lactic dehydrogenase enzymes. (Table II.) Under cyclopropane anesthesia, preliminary laparotomy revealed a liver normal in color and consistency with no evidence of tumor either in the liver or at the nephrectomy site. Liver biopsy demonstrated no parenchymal inflammation, necrosis, or Vol.
110,
Seplembr~u
1965
131. The reported cases follow a similar pattern. Often they are diagnostic problems that have presented months of unexplained fever, progressive weight loss, fatigue, and anemia. Hepatosplenomegaly is sometimes present. Finally, the discovery of an abdominal mass or the appearance of hypercalcemia precipitates a complete laboratory investigation which exposes the hepatopathy. When the liver biopsy shows nonspecific changes, little further attention is paid the hepatic dysfunction because the patient does not symptomatically reflect the chemical abnormalities. The full laboratory picture reveals abnormal values for serum alkaline phosphatase, bromsulphalein retention, flocculation tests, prothrombin time, and serum protein electrophoresis. Later, a phase of transaminase and lactic dehydrogenase enzyme elevations may occur. Serial determinations of these tests demonstrate marked variation which is diagnostically more important than the magnitude of the abnormalities per se. The possibility that anicteric hepatitis, either serum or infectious, caused the hepatopathy observed is not supported by histopathologic examination of the serial liver biopsies ob-
Lemmon, Holland, and Holland
490
FIG. 2. Pulmonary tomography. Serial tomograms metastases over a five month period.
demonstrate
the rapid growth of the solitary pulmonary
FIG. 3. Intravenous pyelogram, retrograde pyelogram and renal arteriogram. The huge left renal mass, the distorted pelvocalyceal collecting system, and the vascular “tumor blush” demonstrate the characteristics of hypernephroma.
tamed. It is unlikely that laboratory abnormalities would immediately improve after anesthesia and surgery or that the observed rapid gains in appetite, weight, and strength would occur in the presence of hepatitis. Two other operable cases demonstrated complete remission of the hepatic dysfunction after removal of the tumor [3,7]. This unusual hepatopathy should not contraindicate the surgical removal of a hypernephroma that would otherwise appear curable, for widespread metastatic disease has not been reported in the cases observed. SUMMARY
AND
CONCLUSIONS
A hypernephroma simulating severe recurrent liver disease is reported and related cases from the literature reviewed. Abnormal values for alkaline phosphatase, prothrombin time,
flocculation tests, protein electrophoresis, bromsulphalein retention, and liver enzymes oxalacetic transaminase, (serum glutamic serum glutamic pyruvic transaminase, lactic dehydrogenase) were found which varied considerably during the course of the illness. No characteristic histopathologic picture was found despite serial liver biopsies. The abnormalvalues returned to normal after removal of the primary tumor and a solitary pulmonary metastasis. The hepatopathy should not be a contraindication to surgery and indeed may aid the diagnostician confronted with a masquerading hypernephroma. REFERENCES
1. BERGER, L. and SINKOFF, M. W. Systemic manifestations of hypernephroma. Am. J. Med., 22: 791, 1957. 2. PINALS, R. S. and KRANE, S. M. Medical aspects of American
Journal
of Surzery
Hepatopathy
of Hypernephroma
renal carcinoma. Postg~ad. 151.J., 38: 507, 1962. 3. Case records of the Massachusetts General Hospital (C!:tse SO-1961 ). Ne%l Eq$and J. Xed., 265: 953, 1961. 4. SHIPMAS, K. H., DOKNING, S. W., and BRADFORD, H. A. Hypernephroma presenting as fever of unknown origin associated with elevated sertml alkaline phosphatase levels. J. l’rol., 89: 160, 1963. 5. STAUFFER,M. H. I\;ephrogenic hepatosplenomegaly. (;nstrornl~roZopy, 40 : 694, 1961. 6. DAVID, S. ,T., VERNER, J. Y., and ENGEI,, F. L. The diagnostic spectrum of hypercalcemia. Am. J. Med., 33 : 88, 1962. 7. TREMRLAY, H. E. and ANSELL, J. S. Carcinoma of the kidney simulating hyperparathyroidism. J. l’rol., 91 : 10, 1964. 8. GOLDRERG. M. F., TASIIJIAX, A. H., JR., ORDER,
Vol. 110, Se~tenzbev
1965
9.
10 11
12.
13.
,491
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