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Extracapillary Tumorous Metastatic Crescents in Glomeruli of the Kidney
Path. Res. Pract. 182, 240-243 (1987)
Extracapillary Tumorous Metastatic Crescents in Glomeruli of the Kidney Tibor T6th M.D. Department of Pathology, County Hospital, Szolnok, Hungary
SUMMARY This report describes intraglomerular tumor cell metastases, as a rare pathologic observation. Specimens of one hundred autopsy cases (each having extrarenal carcinoma) were examined by light microscopy, and in seven of them metastatic crescents were found in the urinary space of the Bowman's capsule. The capsule itself and the layer of the parietal epithelium seemed to be intact. Glomeruli with metastases in five cases were near or inside the extraglomerular metastatic tumor mass. This phenomenon must be distinguished from metaplastic transformation of the glomerular capsular epithelium.
Introduction Intraglomerular metastasis is a rarely observed phenomenon. Two different pathologic patterns of intraglomerular metastatic spread, i.e., intracapillary and extracapillary are distinguished in the literature2, 3, 14, 15. Some studies mention that metastatic tumor cells may be found in the glomerular urinary space, imitating glomerular crescents2, 13. This article presents the clinical, laboratory and morphologic study of seven cases of metastatic glomerular crescents in one hundred tumorous autopsy cases.
Material and Methods One hundred extrarenal tumorous autopsy cases were examined independent of evident renal metastases. For light microscopic study kidney tissue fragments were fixed in 10% formalin. All sections of paraffin-embedded tissue were stained with hematoxylin-eosin, periodic acid-Schiff (PAS), Goldner's trichrom, Endes's trichrom and Jones's silver method. One hundred glomeruli were examined in each case. We compared the primary tumor's histological and cytological characteristics with those of the intraglomerular renal metastases. 0344-0338/87/0182-0240$3.50/0
Results Kidney sections of one hundred patients who died with extrarenal carcinoma were studied. The localization of primary tumors is presented in Table 1. Extracapillary
Table 1. Organ localization of 100 primary carcinomas examined Organ
No.
Bronchus Stomach Liver Colon-rectum Endometrium Mammary glands Pancreas Gall bladder Prostate glands Ovary Esophagus Testis Cervix Urinary bladder
26
10 9 8 8 7 7 4 4 4 4 3 3 3
© 1987 by Gustav Fischer Verlag, Stuttgart
Extracapillary Tumorous Metastatic Crescents . 241 Table 2. Main pathological and clinical data of seven metastatic patients Patient
Age (year)
Sex
Site of the primary tumor
Histologic type Macroscopic kidney metastases
1
69
m
Bronchus
Oat cell carcinoma
+
2
67
m
Bronchus
+
3
61
m
Bronchus
4
50
m
Breast
5
58
f
Breast
Highly differentiated epidermoid carcinoma Poorly differentiated epidermoid carcmoma Tubular carcinoma Infiltrating ductal carcinoma
6
56
m
" Esophagus
7
70
m
Pancreas
Metastatic sites Percentage of tumorous glomeruli
Result of urinalysis
lymph nodes, pancreas, brain, adrenal glands lymph nodes lungs
2
normal
5
normal
-
lymph nodes bones
+
lymph nodes 10 liver, epidermis lymph uodes 7 liver adrenal glands lymph nodes 25 pancreas, lungs lymph nodes 2 liver, lungs
+
Squamous cell carcinoma Adenocarcinoma +
30
proteinuria normal normal proteinuria normal
glomerular metastases were found in seven of one hundred cases. Clinical and pathologic data are summarized in Table 2. In each of seven cases numerous organ and lymph node metastases were found. Renal metastases were not observed in two cases macroscopically (cases 3 and 6). Glomeruli, containing tumor cells, in the remaining five
cases were situated not far from metastatic focuses or in the metastatic tumor mass (Fig. 1). Crescents in the extracapillary space are formed by these tumor cells and the Bowman's capsule is lined sporadically by them (Fig. 2). Metastatic crescents seldom extend from the glomerular vascular pole to encompass the inner surface of
Fig. 1. Case 2. A glomerulus surrounded by small cell bronchogenic carcinoma metastasis. Tumor cells are observed in the Bowman's space. (PAS-stain. x 300)
Fig. 2. Case 2. Relatively intact glomerulus in a metastatic focus containing numerous tumor cells in the glomerular urinary space. Primary tumor: bronchogenic epidermoid carcinoma. (PAS-stain. x 150)
242 . T. T6th
collapsed, normocellular and free from neoplastic cells. Rupture of glomerular capillary loops has not been found. Tumor cells were observed in tubular and vascular lumens and in the interstitium as well. Milde proteinuria was present in two cases only (cases No.2 and 6). The highest % of metastatic glomerular crescents was detected in these cases. Renal function tests and the microscopy of the urine were all normal.
Discussion
Fig. 3. Case 6. A crescent of keratinizing squamous cell esophagic carcinoma cells can be seen in the Bowman's space protruding into the proximal tubule. (Hematoxylin-Eo sin-stain. X 450)
.
the capsule entirely (Fig. 3). The glomerular urinary space is often dilated. High-power view of the glomerulus shows that the neoplastic cells may line the Bowman's capsule in a multilayered fashion in some places, leaving a healthy, viable-appearing glomerular capillary network in the centre (Fig. 4). The glomerular tufts were ischaemic and
Despite the rarity of glomerular metastases, tumor cell emboli are more often seen4, 15, 16. Tumor emboli lodge in glomeruli in about 5% of patients with metastatic carcinoma 15 • Galloway and Ray7 reported the case of a patient with hypernephroma with numerous intraglomerular metastases (80%) to the opposite kidney resulting in renal failure. In seven of our one hundred patients were detected intraglomerular tumor cells in the extra capillary space. Otir material included three squamous cell carcinomas, one oat cell carcinoma, one tubular carcinoma, one infiltrating ductal carcinoma and one adenocarcinoma. In the literature we couldn't find cases with intraglomerular metastases in origin of breast, esophagus or pancreas cancers. The first such case was reported by Lauterburg8 in 1919. He observed metastatic cells of bronchogenic carcinoma in glomeruli. In a peculiar case of multicentric primary carcinoma of the kidney, reported by Lisa 9 , a single glomerulus in a single section showed similar replacement of the capsular epithelium by a layer of tumor cells. In a case of bronchogenic squamous cell carcinoma ROSS13 found similar results to our cases in 1966. In
a
Fig. 4. Case 5. Metastatic tumor cells originating from an infiltrating ductal carcinoma of breast lining the basement membrane of a Bowman's capsule. (a. Jones's silver impregnation, b. Goldner's trichromestain. X 500)
Extracapillary Tumorous Metastatic Crescents . 243
Allen's second edition 1 a similar case is described. All that is said that "foci of adenocarcinoma may lodge in Bowman's space and may be misinterpreted as hyperplastic and hypertrophic parietal epithelium of Bowman's capsule" . Belghiti et al. 2 reported two cases of glomerular metastases. They found in their second case intra- and extracapillary metastases. The primary tumor was ovarial papillary adenocarcinoma. The exact pathomechanism of intraglomerular metastasis is not yet clear. Intra renal metastatic spread could result from at least three mechanisms: first, intralymphatic invasion, although lymphatics have not been described in the glomerular tufts 10; second, intravascular spread from either the arterial or the venous side; third, direct penetration of the tumor cells through Bowman's capsule, although its basement membrane seems to be intact. Proteinuria is, by far, the most important diagnostic sign of glomerular basement membrane injury. Wagle et al. 14 found proteinuria in each of their cases, sometimes in association with microscopic hematuria. But proteinuria was observed only in two of our patients. The differential diagnosis between the metastatic and glomerulonephritic crescents is not difficult. Diagnostic problem may arise only concering the metaplasia of the epithelium of Bowman's capsule. Eisen5 was the first who described adenomatoid metaplasia of the glomerular capsular epithelium. Subsequent reports have illustrated a remarkably similar glomerular epithelial change3, 6, 12, 15. Although the available data indicate that glomerular metaplasia occurs invariably in conjunction with a malignant tumor and almost always with hepatic involvement. The significance of these relationships is unknown. The alteration consists of replacement of the normally flattened epithelial layer of Bowman's capsule by tightly packed columnar or cuboidal epithelium. These cells aren't metastatic tumorous cells. The real tumorous metastatic cells always cover the normal parietal epithelial
cells of glomeruli what can be detected by light microscopy. Mareepo proved experimentally that mmor cells are not attached to the apical side of the epithelium. The namre of this lesion is also unclear.
References 1 Allen AC (1962) The kidney. Grune and Stratton, New York, p. 34 2 Belghiti D, Hirbec G, Bernaudin JF, Periente EA, Martin N (1984) Intraglomerular metastases. Cancer 54: 2309-2312 3 Chappel RH, Phillips JR (1950) Adenomatoid changes of renal capsular epithelium associated with adrenal tumor. Arch Pathol 49: 70-72 4 Datta BN (1978) Intraglomerular metastasis. Indian J Pathol Microbiol 21: 184-185 5 Eisen HN (1946) Adenomatoid transformation of the glomerular capsular epithelium. Am J Parhol 22:597-601 6 Finckh ES, Joske RA (1954) The occurence of columnar epithelium in Bowman's capsule. J Pathol Bacteriol 68: 656-658 7 Galloway NC, Ray CT (1964) Diffuse glomerular metastases from hypernephroma. Arc Intern Med 114: 803-805 8 Lauterburg A (1919) Ober die Ausbreitungswege metastatischer Karzinome in den Nieren. Ztschr Krebsforsch 16: 442-470 9 Lisa JR (1945) Multicentric bilateral carcinoma of the kidnets. Am J Pathol21: 383-385 o Mareel M (1980) Recent aspects of tumour invasiveness.lnt Rev Exp Pathol 22: 65-129 11 Peirce EC (1944) Renal lymphatics. Anat rec 90: 315-335 12 Reidbord HE (1968) Metaplasia of the parietal layer of Bowman's capsule. Am J Clin Pathol 50: 240-242 13 Ross L (1962) Bronchogenic squamous cell carcinoma metastasizing to Bowman's capsule. J Clin Patholl9: 375-377 14 Wagle DG, Moore RH, Murphy GR (1975) Secondary carcinomas of the kidney. J Uroll14: 30-32 15 Ward AM (1970) Tubular metaplasia in Bowman's capsule. J Clin Pathol 23: 472-474 16 Wuketich S (1960) Diffuse intraglomerular metastasis in malignant melanoblastoma. Oncologia 13: 355-363
Received July 14, 1986 . Accepted in revised form September 22, 1986
Key words: Extrarenal carcinoma - Kidney metastasis - Intraglomerular metastasis - Glomerular crescents proteinuria Dr. Tibor Toth, Department of Pathology, County Hospital, Szolnok, POB. 2, Voros Hadsereg u. 39-41 sz., 5004 Szolnok, Hungary
Extracapillary Tumorous Metastatic Crescents in Glomeruli of the Kidney Tibor T6th M.D. Department of Pathology, County Hospital, Szolnok, Hungary
SUMMARY This report describes intraglomerular tumor cell metastases, as a rare pathologic observation. Specimens of one hundred autopsy cases (each having extrarenal carcinoma) were examined by light microscopy, and in seven of them metastatic crescents were found in the urinary space of the Bowman's capsule. The capsule itself and the layer of the parietal epithelium seemed to be intact. Glomeruli with metastases in five cases were near or inside the extraglomerular metastatic tumor mass. This phenomenon must be distinguished from metaplastic transformation of the glomerular capsular epithelium.
Introduction Intraglomerular metastasis is a rarely observed phenomenon. Two different pathologic patterns of intraglomerular metastatic spread, i.e., intracapillary and extracapillary are distinguished in the literature2, 3, 14, 15. Some studies mention that metastatic tumor cells may be found in the glomerular urinary space, imitating glomerular crescents2, 13. This article presents the clinical, laboratory and morphologic study of seven cases of metastatic glomerular crescents in one hundred tumorous autopsy cases.
Material and Methods One hundred extrarenal tumorous autopsy cases were examined independent of evident renal metastases. For light microscopic study kidney tissue fragments were fixed in 10% formalin. All sections of paraffin-embedded tissue were stained with hematoxylin-eosin, periodic acid-Schiff (PAS), Goldner's trichrom, Endes's trichrom and Jones's silver method. One hundred glomeruli were examined in each case. We compared the primary tumor's histological and cytological characteristics with those of the intraglomerular renal metastases. 0344-0338/87/0182-0240$3.50/0
Results Kidney sections of one hundred patients who died with extrarenal carcinoma were studied. The localization of primary tumors is presented in Table 1. Extracapillary
Table 1. Organ localization of 100 primary carcinomas examined Organ
No.
Bronchus Stomach Liver Colon-rectum Endometrium Mammary glands Pancreas Gall bladder Prostate glands Ovary Esophagus Testis Cervix Urinary bladder
26
10 9 8 8 7 7 4 4 4 4 3 3 3
© 1987 by Gustav Fischer Verlag, Stuttgart
Extracapillary Tumorous Metastatic Crescents . 241 Table 2. Main pathological and clinical data of seven metastatic patients Patient
Age (year)
Sex
Site of the primary tumor
Histologic type Macroscopic kidney metastases
1
69
m
Bronchus
Oat cell carcinoma
+
2
67
m
Bronchus
+
3
61
m
Bronchus
4
50
m
Breast
5
58
f
Breast
Highly differentiated epidermoid carcinoma Poorly differentiated epidermoid carcmoma Tubular carcinoma Infiltrating ductal carcinoma
6
56
m
" Esophagus
7
70
m
Pancreas
Metastatic sites Percentage of tumorous glomeruli
Result of urinalysis
lymph nodes, pancreas, brain, adrenal glands lymph nodes lungs
2
normal
5
normal
-
lymph nodes bones
+
lymph nodes 10 liver, epidermis lymph uodes 7 liver adrenal glands lymph nodes 25 pancreas, lungs lymph nodes 2 liver, lungs
+
Squamous cell carcinoma Adenocarcinoma +
30
proteinuria normal normal proteinuria normal
glomerular metastases were found in seven of one hundred cases. Clinical and pathologic data are summarized in Table 2. In each of seven cases numerous organ and lymph node metastases were found. Renal metastases were not observed in two cases macroscopically (cases 3 and 6). Glomeruli, containing tumor cells, in the remaining five
cases were situated not far from metastatic focuses or in the metastatic tumor mass (Fig. 1). Crescents in the extracapillary space are formed by these tumor cells and the Bowman's capsule is lined sporadically by them (Fig. 2). Metastatic crescents seldom extend from the glomerular vascular pole to encompass the inner surface of
Fig. 1. Case 2. A glomerulus surrounded by small cell bronchogenic carcinoma metastasis. Tumor cells are observed in the Bowman's space. (PAS-stain. x 300)
Fig. 2. Case 2. Relatively intact glomerulus in a metastatic focus containing numerous tumor cells in the glomerular urinary space. Primary tumor: bronchogenic epidermoid carcinoma. (PAS-stain. x 150)
242 . T. T6th
collapsed, normocellular and free from neoplastic cells. Rupture of glomerular capillary loops has not been found. Tumor cells were observed in tubular and vascular lumens and in the interstitium as well. Milde proteinuria was present in two cases only (cases No.2 and 6). The highest % of metastatic glomerular crescents was detected in these cases. Renal function tests and the microscopy of the urine were all normal.
Discussion
Fig. 3. Case 6. A crescent of keratinizing squamous cell esophagic carcinoma cells can be seen in the Bowman's space protruding into the proximal tubule. (Hematoxylin-Eo sin-stain. X 450)
.
the capsule entirely (Fig. 3). The glomerular urinary space is often dilated. High-power view of the glomerulus shows that the neoplastic cells may line the Bowman's capsule in a multilayered fashion in some places, leaving a healthy, viable-appearing glomerular capillary network in the centre (Fig. 4). The glomerular tufts were ischaemic and
Despite the rarity of glomerular metastases, tumor cell emboli are more often seen4, 15, 16. Tumor emboli lodge in glomeruli in about 5% of patients with metastatic carcinoma 15 • Galloway and Ray7 reported the case of a patient with hypernephroma with numerous intraglomerular metastases (80%) to the opposite kidney resulting in renal failure. In seven of our one hundred patients were detected intraglomerular tumor cells in the extra capillary space. Otir material included three squamous cell carcinomas, one oat cell carcinoma, one tubular carcinoma, one infiltrating ductal carcinoma and one adenocarcinoma. In the literature we couldn't find cases with intraglomerular metastases in origin of breast, esophagus or pancreas cancers. The first such case was reported by Lauterburg8 in 1919. He observed metastatic cells of bronchogenic carcinoma in glomeruli. In a peculiar case of multicentric primary carcinoma of the kidney, reported by Lisa 9 , a single glomerulus in a single section showed similar replacement of the capsular epithelium by a layer of tumor cells. In a case of bronchogenic squamous cell carcinoma ROSS13 found similar results to our cases in 1966. In
a
Fig. 4. Case 5. Metastatic tumor cells originating from an infiltrating ductal carcinoma of breast lining the basement membrane of a Bowman's capsule. (a. Jones's silver impregnation, b. Goldner's trichromestain. X 500)
Extracapillary Tumorous Metastatic Crescents . 243
Allen's second edition 1 a similar case is described. All that is said that "foci of adenocarcinoma may lodge in Bowman's space and may be misinterpreted as hyperplastic and hypertrophic parietal epithelium of Bowman's capsule" . Belghiti et al. 2 reported two cases of glomerular metastases. They found in their second case intra- and extracapillary metastases. The primary tumor was ovarial papillary adenocarcinoma. The exact pathomechanism of intraglomerular metastasis is not yet clear. Intra renal metastatic spread could result from at least three mechanisms: first, intralymphatic invasion, although lymphatics have not been described in the glomerular tufts 10; second, intravascular spread from either the arterial or the venous side; third, direct penetration of the tumor cells through Bowman's capsule, although its basement membrane seems to be intact. Proteinuria is, by far, the most important diagnostic sign of glomerular basement membrane injury. Wagle et al. 14 found proteinuria in each of their cases, sometimes in association with microscopic hematuria. But proteinuria was observed only in two of our patients. The differential diagnosis between the metastatic and glomerulonephritic crescents is not difficult. Diagnostic problem may arise only concering the metaplasia of the epithelium of Bowman's capsule. Eisen5 was the first who described adenomatoid metaplasia of the glomerular capsular epithelium. Subsequent reports have illustrated a remarkably similar glomerular epithelial change3, 6, 12, 15. Although the available data indicate that glomerular metaplasia occurs invariably in conjunction with a malignant tumor and almost always with hepatic involvement. The significance of these relationships is unknown. The alteration consists of replacement of the normally flattened epithelial layer of Bowman's capsule by tightly packed columnar or cuboidal epithelium. These cells aren't metastatic tumorous cells. The real tumorous metastatic cells always cover the normal parietal epithelial
cells of glomeruli what can be detected by light microscopy. Mareepo proved experimentally that mmor cells are not attached to the apical side of the epithelium. The namre of this lesion is also unclear.
References 1 Allen AC (1962) The kidney. Grune and Stratton, New York, p. 34 2 Belghiti D, Hirbec G, Bernaudin JF, Periente EA, Martin N (1984) Intraglomerular metastases. Cancer 54: 2309-2312 3 Chappel RH, Phillips JR (1950) Adenomatoid changes of renal capsular epithelium associated with adrenal tumor. Arch Pathol 49: 70-72 4 Datta BN (1978) Intraglomerular metastasis. Indian J Pathol Microbiol 21: 184-185 5 Eisen HN (1946) Adenomatoid transformation of the glomerular capsular epithelium. Am J Parhol 22:597-601 6 Finckh ES, Joske RA (1954) The occurence of columnar epithelium in Bowman's capsule. J Pathol Bacteriol 68: 656-658 7 Galloway NC, Ray CT (1964) Diffuse glomerular metastases from hypernephroma. Arc Intern Med 114: 803-805 8 Lauterburg A (1919) Ober die Ausbreitungswege metastatischer Karzinome in den Nieren. Ztschr Krebsforsch 16: 442-470 9 Lisa JR (1945) Multicentric bilateral carcinoma of the kidnets. Am J Pathol21: 383-385 o Mareel M (1980) Recent aspects of tumour invasiveness.lnt Rev Exp Pathol 22: 65-129 11 Peirce EC (1944) Renal lymphatics. Anat rec 90: 315-335 12 Reidbord HE (1968) Metaplasia of the parietal layer of Bowman's capsule. Am J Clin Pathol 50: 240-242 13 Ross L (1962) Bronchogenic squamous cell carcinoma metastasizing to Bowman's capsule. J Clin Patholl9: 375-377 14 Wagle DG, Moore RH, Murphy GR (1975) Secondary carcinomas of the kidney. J Uroll14: 30-32 15 Ward AM (1970) Tubular metaplasia in Bowman's capsule. J Clin Pathol 23: 472-474 16 Wuketich S (1960) Diffuse intraglomerular metastasis in malignant melanoblastoma. Oncologia 13: 355-363
Received July 14, 1986 . Accepted in revised form September 22, 1986
Key words: Extrarenal carcinoma - Kidney metastasis - Intraglomerular metastasis - Glomerular crescents proteinuria Dr. Tibor Toth, Department of Pathology, County Hospital, Szolnok, POB. 2, Voros Hadsereg u. 39-41 sz., 5004 Szolnok, Hungary