False positive linear fluorescence in acute tubular necrosis

H U M A N P A T H O L O G Y - - - V O L U M E 12, NUMBER 11 November 1981

Correspondence FALSE POSITIVE LINEAR FLUORESCENCE IN ACUTE TUBULAR NECROSIS

NODULAR TRANSFORMATION OF THE LIVER, ALPHA-FETOPROTEIN, AND HEPATOCELLULAR CARCINOMA

T o TIlE EDITOR:

T o TIlE EDITOR: In their article Stromeyer and Ishak I raise the possibility that nodular transformation o f the liver could be a prem a l i g n a n t d i s o r d e r , since the h e p a t o c y t e s o f t e n are dysplastic in this disorder, and they think it could be of interest to know whether antigenic markers such as alphafetoprotein are present in such cases. I would like to present a case o f nodular transformation o f the liver that progressed to a hepatocellular carcinoma in which high levels o f alpha-fetoprotein were found before the diagnosis o f carcinoma was established and before the carcinoma developed. A w o m a n a g e d 35 p r e s e n t e d in May 1980 with hematemesis and shock. She had employed orally administered contraceptives for three )'ears. She had no history o f alcohol abuse. Esophagoscopy revealed bleeding varices. T h e liver function test results were all normal, and a transcutaneous liver biopsy specimen was classed as normal. However, the level of alpha-fetoprotein was 1000 ng. per ml. No sign o f a tumor o f the liver could be found by ultrasound examination o f the liver. Because the bleeding from the esophagus continued, a portal-systemic shunt operation was carried out. The liver had a nodular surface, but the consistency was normal. There were no signs of tumor. A surgical biopsy specimen revealed nodular transformation o f the liver with some degree o f dysplasia but no carcinoma. T h e patient did well after the operation, but during the next three years the alpha-fetoprotein level increased from 1500 ng. per ml. (shortly after the operation) to 500,000 ng. per ml. in May 1981. In April 1981 she had become tired, and in May 1981 icterus developed. Ultrasound examination o f the liver revealed a diffuse tumor, and a chest x-ray film showed signs o f metastases. In J u n e 1981 she died, and autopsy revealed a nodular carcinoma o f the liver with a trabecular pattern. T h e r e were metastases to the lungs. T h e disease was found diffusely in the liver, but nodular transformation could not be identified with certainty because most all o f the liver was infiltrated with carcinoma. No other malignant disease was found. T.hat orally administered contraceptives can induce n o d u l a r transformation o f the liver has been d e m o n strated, t but the case presented here is the first in which the alpha-fetoprotein level has been elevated and in which the level has been followed continuously and hepatocellular carcinoma developed. T h e consequence must be that when the diagnosis o f nodular tranformation o f the liver has been established, follow-up evaluations should include radiologic examination and serial alpha-fetoprotein. POOL ERIK SOGAARD, M.D.

Aarhus Denmark 1. Stromeyer, F.W., and Ishak, K.G': Nodular transformation (nodular "regenerative" hyperplasia) of the liver, Hum. Pathol., 12:60-71, 1981.

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Linear deposition o f i m m u n o g l o b u l i n s along peripheral capillary walls is considered to be a typical feature o f antiglomerular basement membrane glomerulonephritis. It is also found in the glomeruli of transplant patients treated with antilymphocyte globulin. In addition, various renal diseases are characterized by the same imm u n o f l u o u r e s c e n c e finding, a h h o u g h p r o p e r controls usually show it to be caused by nonspecific deposition. These cases o f false positive linear deposition o f immunoglobulins in the glomeruli include some cases of systemic lupus erythematosus I and diabetes mellitus, 2 as well as occasional cases of minimal change disease, endotheliomesangial glomerulonephritis, nonspecific glomerulosclerosis, acute interstitial nephritis, and acute transplant rejection. 3 Since the distinction between specific and nonspecific linear deposition o f immunoglobulins has important consequences in the management o f renal diseases, the identification o f problem cases in this respect is a significant issue. We should like to describe linear deposition in a case o f acute tubular necrosis. A 20 )'ear old black male was admitted to the hospital with an infectious illness characterized by high fever, chills, headaches, vomiting, nonbloody diarrhea, aud a nonpruritic papular rash. He did not appear dehydrated. T h e blood pressure was 120/70 ram. Hg. T h e initial blood urea nitrogen and creatinine levels were 32 and 3.4 mg. per dl., respectively. Urinalysis revealed a 2+ protein level, a few white cells and red cells per high power field, and hyaline and granular casts. T h e r e were no red cell casts. In the hospital he was severely oliguric. T h e blood urea nitrogen and creatinine levels rose to 135 and 10.3 mg. per dl., respectively, and hemodialysis was begun. Fever persisted, and bilateral lower lobe consolidation was noted on chest x-ray examination. Intensive investigations, including bacterial cultures, viral titers, leptospira serology, and immunologcical studies, yielded negative findings. An antiglomerular basement membrane antibody determination, as measured by indirect immunofluorescence, was negative. T h e patient was treated intravenously with antibiotics and gradually improved. T h e urine output increased and hemodialysis was discontinued. At this time a percutaneous renal biopsy was performed. He full)' recovered and was discharged three weeks after admission with a blood urea nitrogen level o f 20 mg. per dl. and a creatinine level o f 1.7 rag. per dl. T h e kidney biopsy showed 21 glomeruli with no significant changes by light and electron microscopy. T h e tubules were affected in a patch)' distribution and sh~wed dilation o f the lumen, karyolysis, regenerating changes with occasional mitotic figures, and focal disruption o f the tubular b a s e m e n t m e m b r a n e . Cryostat sections incubated with FITC conjugated antibodies (Behring) resulted in diffuse and global IgG linear staining o f peripheral capillary loops (Fig 1A). In addition, there was evidence of weak granular mesangial staining for C3. Staining for IgM, IgA, and fibrin was negative. When sections were stained with F1TC conjugated antialbumin, a linear pattern, identical to that o f IgG, was observed (Fig 1B). No significant glomerular changes in

CORRESPONDENCE

MASSIVE POSTPARTUM CORPUS LUTEUM CYST T o TIlE EDITOR: ' ~"~

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With regard to the recent report o f a massive postpartum corpus luteum cyst, t we would like to call attention to our recently reported series o f eight similar cases. 2 We interpret the case o f Kott and Schmidt as a luteinized follicle cyst rather than a corpus luteum cyst, because, like o u r cases, it did not have the architectural features (granulosa and theca lutein layers) or cytological features (hyaline bodies and foci o f calcification) that should be found in a corpus luteum o f pregnancy. Also, in one o f o u r cases the corpus luteum o f pregnancy was identified independently o f the cyst.

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PtIILIP B. CLEMENT, M9 Vancouver General Hospital Vancouver, British Columbia Canada

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ROBERT E. SCULLY, M.D. Massachusetts General Hospital Boston, Massachusetts

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Figure 1. A (above), linear deposition of IgG along peripheral capillary loops. B (below), linear deposition of albumin with pattern identical to IgG. (FITC--antihuman albumin. A, x268. B, • the peripheral capillary loops were observed by electron microscopy. T h e morphological changes were interpreted as tilose o f acute tubular necrosis o f the tubulorrhectic type and were related to sepsis demonstrated clinically, although no specific cause for it was found. T h e fact that a nonimm u n o l o g i c a l r e a c t a n t such as a l b u m i n gave a linear peripheral pattern identical to that o f IgG suggests that this finding is a false positive one, probably representing insudation o f plasma proteins between the endothelium and the glomerular basement membrane. This emphasizes the need to include staining for nonimmunological proteins in the routine investigation of renal biopsy specimens, which should help to avoid confusion between false positive and true linear deposition found in antiglomerular basement membrane antibody disease. Since acute tubular necrosis is a frequent postmortem finding, it is likely to represent an important cause o f linear patterns'in kidney glomeruli at autopsy 9 SERGE JOTIIV, M.D., Ph.D. ~[URRAY VASILEVSKY, M . D .

Departments o f Pathology and Medicine McGill University Royal Victoria Hospital Montreal, Quebec Canada I. Koffler, D., Agnello, V., Carr, l., and Kunkel, tt. G.: Variable patterns of immunoglobulin and complement deposition in the kidneys of patients with systemic lupus erythematosus. Am. J. Path. 56:305, 1969. 2. McCluskey, R.T.: The value of immunofluorescence in the study of human renal disease. J. Exp. Med., 134:242, 1971. 3. Zollinger, H. U., and Mihatsch, M. J. In Renal Pathology in Biopsy. Berlin, Springer Verlag, 1978.

1. Kon, M. M., and Schmidt, W.A. Massive Ix)stpartum corpus luteum cyst: a case report. Hum. Pathol., 12:468, 1981. 2. Clement, P. B., and Scully, R. E.: Large solitary luteinized follicle cyst of pregnancy and puerperium. A clinicopathological analysis of eight cases. Am. J. Surg. Pathol., 4:431, 1980.

POLYKARYOCYTES RESEMBLING WARTHIN-FINKELDEY GIANT CELLS T o TIlE EDITOR: We read with interest tile article by Kjeldsberg and Kim * concerning the identification o f polykaryocytes resembling Warthin-Finkeldey giant cells in reactive and neoplastic lymphoid disorders. We observed cells similar to those described by these authors in 67 cases o f lymphoid disorders? None of these patients presented with measles infection. In reactive lymphoid proliferations (34 cases) these Warthin-Finkeldey-like cells were identified more frequently in germinal centers than in interfollicular areas. In neoplastic lymphoid disorders (33 cases) such cells were found in 19 cases o f Hodgkin's disease. In the stud)' by Kjeldsberg and Kim, 12 cases o f Hodgkin's disease showed polykaryocytes. In their nine cases of lymphocytic predominance it would be o f interest to know whether these cases are nodular or diffuse forms o f the disease. Indeed, in o u r stud)', 14 o f the 17 cases o f Hodgkin's disease with l y m p h o c y t i c p r e d o m i n a n c e ( n o d u l a r type) e x h i b i t e d Warthin-Finkeldey-like cells. T h e clustering of these cells in one area, as mentioned by these authors, was clearly recognized in some o f these lesions. We agree with these authors about the identification o f polykaryocytes in malignant iymphomas o f low grade malignancy. All our 13 cases o f lymphomas according to the Kiel classification were o f a low grade malignancy? Furthermore, immunoperoxidase and electron microscopic examinations have not enabled us to elucidate the nature o f these cells. As Kjeldsberg and Kim pointed out, the immunoperoxidase technique perforined in five o f o u r cases did not demonstrate immunoglobulin lysozyme or antichymotrypsin in these cells. However, it seemed that

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