RETROPERITONEAL FIBROSIS AS HOST RESPONSE TO PAPILLARY RENAL CELL CARCINOMA FRANK B. FROMOWITZ, M.D. FREDERICK MILLER, M.D.
From the Department of Pathology, School of Medicine and University Hospital, State University of New York at Stony Brook, New York
ABS TRA C T--A case of papillary renal cell carcinoma associated with retroperitoneal fibrosis is described. This type of fibrosis has not been previously reported to be associated with renal cell carcinoma. The case is of additional interest in that it implicates an immune phenomenon in the pathogenesis of the fibrosis, involving both putative tumor antigens and antigens associated with tumor growth but unrelated to tumor cells.
~inhe the initial case report of retroperitoneal ~ibmsis by Albarran in 19051 .and the classic ~ieseription by Ormond in 1948, 2 there have ~een more than 500 instances described in the ~ft~rature.3 Of these, less than 10 percent have • " with malignancy, and among is no instance of a renal cell 'ring at the same time as the 4 Mthough the basic process causation at the present time, !ng bits of evidence which sugmechanism. 5-7 ry carcinoma is a subset of of the kidney which accounts 'cent of eases, s It has a rather logic appearance, and studies ravesuggested a more favorable outcome than ith~r types of cancer in this organ, s,° We report tease of renal papillary carcinoma associated ith retroperitoneal fibrosis and suggest that e fibrosis is an exaggerated host response to ~mOr-associated antigens and that the fibrosis ~i~ybe related to the better prognosis of papilI~rYrenal cell carcinoma•
lambda light chains and to gamma, mu, and alpha heavy chains (DAKO, Santa Barbara, CA) were applied to tissue sections which had been subject to deparaffinization, trypsin digestion (30 min.), hydrogen peroxide-methanol quenching, and incubation with normal swine serum. Primary antisera were incubated overnight at 4 o C. Goat anti-rabbit immunoglobulin antiserum, used as a bridge, was applied followed by rabbit PAP complex and DAB reagent (10 rain.) Immunofluorescent studies for anti-kidney antibodies were performed using both frozen murine kidney sections and deparaffinized formalin-fixed paraffin-embedded tissue from the patient's own resected kidney. After washing the sections with saline, they were overlain with dilutions of the patient's sera, incubated, washed with saline, and visualized by incubation with fluorescein-labeled goat anti-human IgG (Kent Laboratories, Vancouver, B.C.). Slides were evaluated using a Zeiss Axiomat fluorescent microscope equipped with epi-illumination.
Material and Methods
Case Report
.!rnrnunoperoxidase studies were performed ~ f0rmalin-fixed paraffin-embedded tissue. !abbit anti-human antisera to kappa and
A sixty-two-year-old white male carpenter with seropositive rheumatoid arthritis, borderline diabetes mellitus, mild exogenous
!i
! oLocy j
SEPTEMBER 1991
/
VOLUME XXXVIII, NUMBER 3
259
FIGURE1. (A) Cortical renal cell carcinoma with dense fibrous capsule. Regions of geographic fibrosis a ~ inflammation in cortex away from tumor are indicated with arrows. (B) Cross section of tumor (left) sh6i~ considerable hemorrhage and thick fibrous capsule showing focus of apparent disruption (arrow). lq'.e~ parenchyma away from tumor (right) shows dense fibrosis that also markedly thickens renal capsule. obesity, and drug-controlled essential hypertension was seen at the Veterans Affairs Hospital, Northport, New York, for recurrent urinary tract infections. Prostatic hyperplasia was treated by transurethral resection. At that time the seminal vesicle on the right side was felt to be indurated. When a needle biopsy revealed only fibrosis and chronic inflammation, a more detailed urinary tract evaluation was conducted. Angiography disclosed an avascular intraparenchymal renal tumor. His laboratory evaluation just prior to surgery disclosed a white count of 11,900 with a normal differential, a hematocrit of 37 percent, and a hemoglobin of 12.5 g/dL. His blood glucose was 215 mg/dL; electrolytes were normal except for potassium 3.2 mEq/L; triglycerides were 243 mg/dL and blood urea nitrogen (BUN) 44 mg/dL with a creatinine of 1.6. All other studies were within physiologic ranges. His physical examination revealed modest arthritic changes, very mild hypertension, and no stigmata of diabetes. He had never received methysergide. A radical nephrectomy was performed. A 5.0-cm spherical cortical tumor with considerable hemorrhage, encapsulated by dense fibrous tissue was found (Fig. 1). Pathologic examination disclosed a papillary adenocarcinoma of clear and granular cell type (Fig. 2A). There was no extrarenal or vascular extension and no gross metastases were observed. The tumor was clearly peripheral and did not in any way obstruct urinary flow. The kidney showed geographic areas of whitish beige discoloration of firm consistency which markedly thickened the renal capsule in involved areas (Fig. 1). On mi-
260
croscopic examination these consisted of regioi of effacing fibrosis intermingled with lymp~io~ infiltrates that foeally included large numb~ of macrophages, plasma cell, and eosinop~ (Fig. 2B). at any
the primary growth. The tumor itself sho~i foei of lymphocytic infiltratio: laden macrophages in the stal processes (Fig. 2D) and ehol calcification adjaeent to area hemorrhage (Fig. 2E). Im studies disclosed no immunog] in the kidney and the patient reactive toward kidney substi had no other evidenee, clinie~ allergic or rheumatic disease. lum and along the ureter exte to the seminal vesicle was p: scopically these regions were e connective tissue with occa minal centers (Fig. 2C). This lateral, ipsilateral to the tumo distinctly different from the munoperoxidase studies in th polyclonality of the plasma c infiltrate. The patient did well posto] ceived no adjuvant therapy, q evidence of recurrence of tun of the retroperitoneal fibros time, five years postoperative
UROLOGY
Comment This ease is of interest in thl it extends the list of tumors
/
S E P T E M B E R 1991
/
VOLUML
. . . . . .
~ilibrosing process involving the retroperito~eurn4 to adenocarcinoma of the kidney. This ~eeurrence has not been reported previously. ~econd, I~'" " it • stren g thens the observ a lt" o nsofMan!~!!!a-Jlmmez e t al. s and others 9 regarding the ~ore favorable prognosis associated with the ~apillary form of renal cell carcinoma. Third, !t tends to focus on a relationship between a i6rrn of tissue response that is likely of immune igin and a potential defense of the body to , ~plasla Retroperltoneal flbr . ' osis is a relatively unI°mmon disorder that belongs to a group of
similar entities termed sclerosing fibrositis or multifocal fibrosclerosis, and includes mediasfinal sclerosis, sclerosing cholangitis, Riedel thyroiditis, and orbital pseudotumor. The great majority of occurrences are idiopathic, s but injury including radiation, drugs, particularly methysergide, 1° certain infections, and malignancy have been implicated. The last accounts for less than 10 percent of cases with common carcinomas and lymphomas being most frequent. Tumors of the urinary system are uncommonly associated, and reported cases have been limited to urothelial carcinomas of
il ~ROLOGy /
SEPTEMBER 1991
/
VOLUME XXXVIII, NUMBER 3
261
the bladder, ureter, and renal pelvis. 11 No cases of renal carcinoma have been reported in conjunction with retroperitoneal fibrosis. However, the kidney may be involved in the sclerosing process as retroperitoneal fibrosis may be confined to perirenal adipose tissue manifesting as a nodular mass that impinges on the kidney. 12 Thus, retroperitoneal fibrosis may present as a localized, unilateral p h e n o m e n o n with the diagnosis dependent on the microscopic appearance of the lesion and the demonstration of lymphoid and plasma cell polyclonality by immunohistologie studies. ~2 The fibrosing process in our case shares the histologic features that define the fibrosing and sclerosing disorders cited previously whether localized or generalized. The similarity in morphology among sclerosing lesions of this type suggests a common pathogenetic mechanism• For example in our case, it is striking how similar the morphology of the fibrosing regions, both in the kidney and in the retroperitoneum, was to that of the thyroid in Reidel struma (Fig. 2B). Recent speculation tends to strengthen the suppositions of Raper 7 and Hoffman and Trippel 6 that an immune phenomenon might be common to all cases. It is certainly of interest to consider recent findings indicating that products of lymphoeytes, ~z,~4 macrophages, ~,~ and mast cells ~7 can induce fibroblastic proliferation. Activation of these cells by immune reactions would be a potential explanation for sclerosis. In the case of papillary carcinoma, it is possible that certain if not most of these tumors release tubular cell antigens. These might function in a manner analogous to those studied by Nielson, Jiminez, and Phillips. TM Those investigators found that renal tubular antigens interacted with mononucler cells, in an experim e n t a l m o d e l of interstitial nephritis, to elaborate soluble mediators that stimulated collagen production. Comparison of papillary adenocarcinomas of the kidney with other renal cell carcinomas has indicated that the former have a significantly better prognosis, are angiographieally hypo- or avascular, tend to be low stage, are more cystic, hemorrhagic, and necrotic, are commonly infiltrated by macrophages, and usually enveloped in a dense fibrous capsule, even if the tumor is of considerable size. s,9 All of these features were noted in the ease reported here. Recent reports suggesting that renal cell eareinomas with papillary features may have a worse prognosis than nonpapillary renal cell
262
UROLOGY
iN
carcinoma 19,~° may involve a different type Q papillary renal cell carcinoma. That is, thl papillary tumors that seem to be prognosticall. favorable are angiographically hypo- or avaseui lar, while the radiographic appearance of th~ poor prognostic group is not described. Avaseui~;i larity may be one of several favorable prognosi tic features in papillary renal cell carcinornl (see below).o The tumor stroma of our cases ani many of those described in the Barnes Hospit~ seriess were focally rich in macrophages, ly~ phocytes, and other inflammatory cells (Fi~ 2D); the transversing vessels were likewisl greatly thickened. The picture is much a k i n ~ that which might occur at any site of chr0~:'~ antigenic stimulation. We would suggest, as H ferred above, that these tumors in many "'~:~-~zina~ viduals retain or. express an. antigenicity w lGi~i ~ . . . allows for immune reactivity and, m turn, c ~ tainment of the tumor. :~ It must be noted, however, that w h e n ~ amined critically the evidence that fibro processes in general and retroperitoneal f i b ~ in particular are immune disorders is r n o s ~ circumstantial. It is true that retroneritoneflilf~i~ brosis may respond to steroids, in a morphology like that seen in im disease, 2~ may b e associated autoimmune conditions, and wlq identified, e.g., methysergide, freq when that substance is disconti observations fit other nonimm with equal facility. However, so dence implicates a vascular injui tion of the fibrosis with the expos component of atherosclerotic pla munogen. 22 By analogy, since renal papillary earci~ may be massively necrotic or h e m o r r ~ fibrous walled, as well as slow growing, i ~ mimic atherosclerotic plaques or atherosd~l abdominal aortic aneurysms in their lon~i~i accumulation of lipid material as shown i quent cholesterol cleft formation and ae lation of foamy histioeYtes within t h e (Fig. 2E). 8 A breech in the wall of the: (Fig. 1B) may then be analogous to disr of the wall of an atherosclerotic vessel in ing previously sequestered lip body's immune system. Since report seemed predisposed to nomena, the antigenic stimuh have provoked a highly exa~ response, one that may be usu and thus not recognizable in
/
SEPTEMBER
1991
/
VOLUME
A........
:
th this type of tumor; that is in other cases the ~irnary manifestation of the sclerosing process ~ay be a thick-walled fibrous tumor capsule ~attogether with hypo- or avascularity hinders ~mor spread. in summary we report a case of papillary re~al cell carcinoma associated with retroperito~eal fibrosis; this occurrence has not previously en noted although retroperitoneal fibrosis ~y in fact, impinge on the kidney as a tumor;e mass. 12 The potential importance of this ikage is presented in regard to the favorable l~rOgnosis associated with this particular type of }renal cell carcinoma and speculation regarding athogenesis of this, and other types of fibrosi,~g disorders is offered.
~i
f
~
D e p a r t m e n t of P a t h o l o g y U n i v e r s i t y H o s p i t a l L - 2 , 756 SUNY at Stony Brook S t o n y B r o o k , N e w York 11794-8691 (DR. FROMOWITZ)
References L Albarran JJ" Retention renale par periureterite liberation et ~4e3nede l'uretere, Assoc France d'Urol 9:5112 (1905). ~:: 2: Ormond IK: Bilateral ureteral obstruction due to envelopby an inflammatory retroperitoneal proc948). dema GD: The clinical significance of ret;urgery 81:250 (1977). td Chisholm GD: Retroperitoneal fibrosis rant disease, Br J Cancer 28:453 (1973). tlsh PC: Idiopathic retroperitoneal fibrosis, ad Trippel OH: Retroperitoneal fibrosis etiJ Urol 86:222 (1964).
SEPTEMBER 1991
/
7. Raper FP: Idiopathic retroperitoneal fibrosis involving the ureters, Br J Urol 28:436 (1956). 8. Mancilla-Jiminez R, Stanley RJ, and Blath RA: Papillary renal cell carcinoma. A clinical, radiologic, and pathologic study of 34 eases, Cancer 38; 2469 (1976). 9. Mydlo JH, and Bard RH: Analysis of papillary renal adenocarcinoma, Urology 30:529 (1987). 10. Utz DC, Rooke ED, Spittell JA Jr, and Bartholomew LG: Retroperitoneal fibrosis in patients taking methysergide, JAMA 191:983 (1965). 11. Reiner I, YachiaD, Nissim F, and Fishelowitz Y: Retroperitoncal fibrosis in association with urothelial tumor, J Urol 132: 115 (1984). 12. Osborn BM, Butler JJ, Bloustein P, and Sumner G: Idiopathic retroperitoneal fibrosis (sclerosing retroperitonitis), Human Pathol 18:735 (1987). 13. Wahl SM, and Gately CL: Modulation of fibroblast growth by a lymphokine of human T cell and continuous T cell line origin, J Immunol 130:1226 (1983). 14. Posthelwaite AE, et ah Characterization of human lymphokine that stimulates fibroblasts to produce collagen (abstr.), Arth Rheum 24:$61 (1981). 15. Kahaleh MB, DeLustro F, Bock W, and LeRoy EC: Human monocyte modulation of endothelial ceils and fibroblast growth: possible mechanisms for fibrosis, Clin Immunol Immunopath 39:242 (1986). 16. Hibbs MD, et ah Alterations in collagen production in mixed mononuclear leukocyte-fibroblast cultures, J Exp Med 157: 47 (1983). 17. Claman HN, Jaffee BD, Huff ]C, and Clark RAF: Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis, Cell Immunol 94:73 (1985). 18. Neilson EG, Jiminez SA, and Phillips SM: Cell mediated immunity in interstitial nephritis, II. T-lymphocyte-mediated fibroblast proliferation and collagen synthesis; an immune mechanism for renal fibrogenesis, J Immunol 125:1708 (1980). 19. Fuhrman SA, Lasky CC, and Limas C: Prognostic significance of morphologic parameters in renal cell carcinoma, Am J Surg Pathol 6:655 (1982). 20. Medeiras LJ, Gelb AB, and Weiss LM: Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases, Cancer 61:1639 (1988). 21. Mitchinson MJ: The pathology of idiopathic retroperitoneal fibrosis, J Clin Pathol 23:681 (1970). 22. Mitchinson MJ: Retroperitoneal fibrosis revisited, Arch Pathol Lab Med 110:784 (1986).
VOLUME XXXVIII, NUMBER 3
263
From the Department of Pathology, School of Medicine and University Hospital, State University of New York at Stony Brook, New York
ABS TRA C T--A case of papillary renal cell carcinoma associated with retroperitoneal fibrosis is described. This type of fibrosis has not been previously reported to be associated with renal cell carcinoma. The case is of additional interest in that it implicates an immune phenomenon in the pathogenesis of the fibrosis, involving both putative tumor antigens and antigens associated with tumor growth but unrelated to tumor cells.
~inhe the initial case report of retroperitoneal ~ibmsis by Albarran in 19051 .and the classic ~ieseription by Ormond in 1948, 2 there have ~een more than 500 instances described in the ~ft~rature.3 Of these, less than 10 percent have • " with malignancy, and among is no instance of a renal cell 'ring at the same time as the 4 Mthough the basic process causation at the present time, !ng bits of evidence which sugmechanism. 5-7 ry carcinoma is a subset of of the kidney which accounts 'cent of eases, s It has a rather logic appearance, and studies ravesuggested a more favorable outcome than ith~r types of cancer in this organ, s,° We report tease of renal papillary carcinoma associated ith retroperitoneal fibrosis and suggest that e fibrosis is an exaggerated host response to ~mOr-associated antigens and that the fibrosis ~i~ybe related to the better prognosis of papilI~rYrenal cell carcinoma•
lambda light chains and to gamma, mu, and alpha heavy chains (DAKO, Santa Barbara, CA) were applied to tissue sections which had been subject to deparaffinization, trypsin digestion (30 min.), hydrogen peroxide-methanol quenching, and incubation with normal swine serum. Primary antisera were incubated overnight at 4 o C. Goat anti-rabbit immunoglobulin antiserum, used as a bridge, was applied followed by rabbit PAP complex and DAB reagent (10 rain.) Immunofluorescent studies for anti-kidney antibodies were performed using both frozen murine kidney sections and deparaffinized formalin-fixed paraffin-embedded tissue from the patient's own resected kidney. After washing the sections with saline, they were overlain with dilutions of the patient's sera, incubated, washed with saline, and visualized by incubation with fluorescein-labeled goat anti-human IgG (Kent Laboratories, Vancouver, B.C.). Slides were evaluated using a Zeiss Axiomat fluorescent microscope equipped with epi-illumination.
Material and Methods
Case Report
.!rnrnunoperoxidase studies were performed ~ f0rmalin-fixed paraffin-embedded tissue. !abbit anti-human antisera to kappa and
A sixty-two-year-old white male carpenter with seropositive rheumatoid arthritis, borderline diabetes mellitus, mild exogenous
!i
! oLocy j
SEPTEMBER 1991
/
VOLUME XXXVIII, NUMBER 3
259
FIGURE1. (A) Cortical renal cell carcinoma with dense fibrous capsule. Regions of geographic fibrosis a ~ inflammation in cortex away from tumor are indicated with arrows. (B) Cross section of tumor (left) sh6i~ considerable hemorrhage and thick fibrous capsule showing focus of apparent disruption (arrow). lq'.e~ parenchyma away from tumor (right) shows dense fibrosis that also markedly thickens renal capsule. obesity, and drug-controlled essential hypertension was seen at the Veterans Affairs Hospital, Northport, New York, for recurrent urinary tract infections. Prostatic hyperplasia was treated by transurethral resection. At that time the seminal vesicle on the right side was felt to be indurated. When a needle biopsy revealed only fibrosis and chronic inflammation, a more detailed urinary tract evaluation was conducted. Angiography disclosed an avascular intraparenchymal renal tumor. His laboratory evaluation just prior to surgery disclosed a white count of 11,900 with a normal differential, a hematocrit of 37 percent, and a hemoglobin of 12.5 g/dL. His blood glucose was 215 mg/dL; electrolytes were normal except for potassium 3.2 mEq/L; triglycerides were 243 mg/dL and blood urea nitrogen (BUN) 44 mg/dL with a creatinine of 1.6. All other studies were within physiologic ranges. His physical examination revealed modest arthritic changes, very mild hypertension, and no stigmata of diabetes. He had never received methysergide. A radical nephrectomy was performed. A 5.0-cm spherical cortical tumor with considerable hemorrhage, encapsulated by dense fibrous tissue was found (Fig. 1). Pathologic examination disclosed a papillary adenocarcinoma of clear and granular cell type (Fig. 2A). There was no extrarenal or vascular extension and no gross metastases were observed. The tumor was clearly peripheral and did not in any way obstruct urinary flow. The kidney showed geographic areas of whitish beige discoloration of firm consistency which markedly thickened the renal capsule in involved areas (Fig. 1). On mi-
260
croscopic examination these consisted of regioi of effacing fibrosis intermingled with lymp~io~ infiltrates that foeally included large numb~ of macrophages, plasma cell, and eosinop~ (Fig. 2B). at any
the primary growth. The tumor itself sho~i foei of lymphocytic infiltratio: laden macrophages in the stal processes (Fig. 2D) and ehol calcification adjaeent to area hemorrhage (Fig. 2E). Im studies disclosed no immunog] in the kidney and the patient reactive toward kidney substi had no other evidenee, clinie~ allergic or rheumatic disease. lum and along the ureter exte to the seminal vesicle was p: scopically these regions were e connective tissue with occa minal centers (Fig. 2C). This lateral, ipsilateral to the tumo distinctly different from the munoperoxidase studies in th polyclonality of the plasma c infiltrate. The patient did well posto] ceived no adjuvant therapy, q evidence of recurrence of tun of the retroperitoneal fibros time, five years postoperative
UROLOGY
Comment This ease is of interest in thl it extends the list of tumors
/
S E P T E M B E R 1991
/
VOLUML
. . . . . .
~ilibrosing process involving the retroperito~eurn4 to adenocarcinoma of the kidney. This ~eeurrence has not been reported previously. ~econd, I~'" " it • stren g thens the observ a lt" o nsofMan!~!!!a-Jlmmez e t al. s and others 9 regarding the ~ore favorable prognosis associated with the ~apillary form of renal cell carcinoma. Third, !t tends to focus on a relationship between a i6rrn of tissue response that is likely of immune igin and a potential defense of the body to , ~plasla Retroperltoneal flbr . ' osis is a relatively unI°mmon disorder that belongs to a group of
similar entities termed sclerosing fibrositis or multifocal fibrosclerosis, and includes mediasfinal sclerosis, sclerosing cholangitis, Riedel thyroiditis, and orbital pseudotumor. The great majority of occurrences are idiopathic, s but injury including radiation, drugs, particularly methysergide, 1° certain infections, and malignancy have been implicated. The last accounts for less than 10 percent of cases with common carcinomas and lymphomas being most frequent. Tumors of the urinary system are uncommonly associated, and reported cases have been limited to urothelial carcinomas of
il ~ROLOGy /
SEPTEMBER 1991
/
VOLUME XXXVIII, NUMBER 3
261
the bladder, ureter, and renal pelvis. 11 No cases of renal carcinoma have been reported in conjunction with retroperitoneal fibrosis. However, the kidney may be involved in the sclerosing process as retroperitoneal fibrosis may be confined to perirenal adipose tissue manifesting as a nodular mass that impinges on the kidney. 12 Thus, retroperitoneal fibrosis may present as a localized, unilateral p h e n o m e n o n with the diagnosis dependent on the microscopic appearance of the lesion and the demonstration of lymphoid and plasma cell polyclonality by immunohistologie studies. ~2 The fibrosing process in our case shares the histologic features that define the fibrosing and sclerosing disorders cited previously whether localized or generalized. The similarity in morphology among sclerosing lesions of this type suggests a common pathogenetic mechanism• For example in our case, it is striking how similar the morphology of the fibrosing regions, both in the kidney and in the retroperitoneum, was to that of the thyroid in Reidel struma (Fig. 2B). Recent speculation tends to strengthen the suppositions of Raper 7 and Hoffman and Trippel 6 that an immune phenomenon might be common to all cases. It is certainly of interest to consider recent findings indicating that products of lymphoeytes, ~z,~4 macrophages, ~,~ and mast cells ~7 can induce fibroblastic proliferation. Activation of these cells by immune reactions would be a potential explanation for sclerosis. In the case of papillary carcinoma, it is possible that certain if not most of these tumors release tubular cell antigens. These might function in a manner analogous to those studied by Nielson, Jiminez, and Phillips. TM Those investigators found that renal tubular antigens interacted with mononucler cells, in an experim e n t a l m o d e l of interstitial nephritis, to elaborate soluble mediators that stimulated collagen production. Comparison of papillary adenocarcinomas of the kidney with other renal cell carcinomas has indicated that the former have a significantly better prognosis, are angiographieally hypo- or avascular, tend to be low stage, are more cystic, hemorrhagic, and necrotic, are commonly infiltrated by macrophages, and usually enveloped in a dense fibrous capsule, even if the tumor is of considerable size. s,9 All of these features were noted in the ease reported here. Recent reports suggesting that renal cell eareinomas with papillary features may have a worse prognosis than nonpapillary renal cell
262
UROLOGY
iN
carcinoma 19,~° may involve a different type Q papillary renal cell carcinoma. That is, thl papillary tumors that seem to be prognosticall. favorable are angiographically hypo- or avaseui lar, while the radiographic appearance of th~ poor prognostic group is not described. Avaseui~;i larity may be one of several favorable prognosi tic features in papillary renal cell carcinornl (see below).o The tumor stroma of our cases ani many of those described in the Barnes Hospit~ seriess were focally rich in macrophages, ly~ phocytes, and other inflammatory cells (Fi~ 2D); the transversing vessels were likewisl greatly thickened. The picture is much a k i n ~ that which might occur at any site of chr0~:'~ antigenic stimulation. We would suggest, as H ferred above, that these tumors in many "'~:~-~zina~ viduals retain or. express an. antigenicity w lGi~i ~ . . . allows for immune reactivity and, m turn, c ~ tainment of the tumor. :~ It must be noted, however, that w h e n ~ amined critically the evidence that fibro processes in general and retroperitoneal f i b ~ in particular are immune disorders is r n o s ~ circumstantial. It is true that retroneritoneflilf~i~ brosis may respond to steroids, in a morphology like that seen in im disease, 2~ may b e associated autoimmune conditions, and wlq identified, e.g., methysergide, freq when that substance is disconti observations fit other nonimm with equal facility. However, so dence implicates a vascular injui tion of the fibrosis with the expos component of atherosclerotic pla munogen. 22 By analogy, since renal papillary earci~ may be massively necrotic or h e m o r r ~ fibrous walled, as well as slow growing, i ~ mimic atherosclerotic plaques or atherosd~l abdominal aortic aneurysms in their lon~i~i accumulation of lipid material as shown i quent cholesterol cleft formation and ae lation of foamy histioeYtes within t h e (Fig. 2E). 8 A breech in the wall of the: (Fig. 1B) may then be analogous to disr of the wall of an atherosclerotic vessel in ing previously sequestered lip body's immune system. Since report seemed predisposed to nomena, the antigenic stimuh have provoked a highly exa~ response, one that may be usu and thus not recognizable in
/
SEPTEMBER
1991
/
VOLUME
A........
:
th this type of tumor; that is in other cases the ~irnary manifestation of the sclerosing process ~ay be a thick-walled fibrous tumor capsule ~attogether with hypo- or avascularity hinders ~mor spread. in summary we report a case of papillary re~al cell carcinoma associated with retroperito~eal fibrosis; this occurrence has not previously en noted although retroperitoneal fibrosis ~y in fact, impinge on the kidney as a tumor;e mass. 12 The potential importance of this ikage is presented in regard to the favorable l~rOgnosis associated with this particular type of }renal cell carcinoma and speculation regarding athogenesis of this, and other types of fibrosi,~g disorders is offered.
~i
f
~
D e p a r t m e n t of P a t h o l o g y U n i v e r s i t y H o s p i t a l L - 2 , 756 SUNY at Stony Brook S t o n y B r o o k , N e w York 11794-8691 (DR. FROMOWITZ)
References L Albarran JJ" Retention renale par periureterite liberation et ~4e3nede l'uretere, Assoc France d'Urol 9:5112 (1905). ~:: 2: Ormond IK: Bilateral ureteral obstruction due to envelopby an inflammatory retroperitoneal proc948). dema GD: The clinical significance of ret;urgery 81:250 (1977). td Chisholm GD: Retroperitoneal fibrosis rant disease, Br J Cancer 28:453 (1973). tlsh PC: Idiopathic retroperitoneal fibrosis, ad Trippel OH: Retroperitoneal fibrosis etiJ Urol 86:222 (1964).
SEPTEMBER 1991
/
7. Raper FP: Idiopathic retroperitoneal fibrosis involving the ureters, Br J Urol 28:436 (1956). 8. Mancilla-Jiminez R, Stanley RJ, and Blath RA: Papillary renal cell carcinoma. A clinical, radiologic, and pathologic study of 34 eases, Cancer 38; 2469 (1976). 9. Mydlo JH, and Bard RH: Analysis of papillary renal adenocarcinoma, Urology 30:529 (1987). 10. Utz DC, Rooke ED, Spittell JA Jr, and Bartholomew LG: Retroperitoneal fibrosis in patients taking methysergide, JAMA 191:983 (1965). 11. Reiner I, YachiaD, Nissim F, and Fishelowitz Y: Retroperitoncal fibrosis in association with urothelial tumor, J Urol 132: 115 (1984). 12. Osborn BM, Butler JJ, Bloustein P, and Sumner G: Idiopathic retroperitoneal fibrosis (sclerosing retroperitonitis), Human Pathol 18:735 (1987). 13. Wahl SM, and Gately CL: Modulation of fibroblast growth by a lymphokine of human T cell and continuous T cell line origin, J Immunol 130:1226 (1983). 14. Posthelwaite AE, et ah Characterization of human lymphokine that stimulates fibroblasts to produce collagen (abstr.), Arth Rheum 24:$61 (1981). 15. Kahaleh MB, DeLustro F, Bock W, and LeRoy EC: Human monocyte modulation of endothelial ceils and fibroblast growth: possible mechanisms for fibrosis, Clin Immunol Immunopath 39:242 (1986). 16. Hibbs MD, et ah Alterations in collagen production in mixed mononuclear leukocyte-fibroblast cultures, J Exp Med 157: 47 (1983). 17. Claman HN, Jaffee BD, Huff ]C, and Clark RAF: Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis, Cell Immunol 94:73 (1985). 18. Neilson EG, Jiminez SA, and Phillips SM: Cell mediated immunity in interstitial nephritis, II. T-lymphocyte-mediated fibroblast proliferation and collagen synthesis; an immune mechanism for renal fibrogenesis, J Immunol 125:1708 (1980). 19. Fuhrman SA, Lasky CC, and Limas C: Prognostic significance of morphologic parameters in renal cell carcinoma, Am J Surg Pathol 6:655 (1982). 20. Medeiras LJ, Gelb AB, and Weiss LM: Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases, Cancer 61:1639 (1988). 21. Mitchinson MJ: The pathology of idiopathic retroperitoneal fibrosis, J Clin Pathol 23:681 (1970). 22. Mitchinson MJ: Retroperitoneal fibrosis revisited, Arch Pathol Lab Med 110:784 (1986).
VOLUME XXXVIII, NUMBER 3
263
