A histomorphologic and ultrastructural study of the malignant tumours of the renal pelvis.N Tyagi, S Sharma, S Tyagi, V Maheshwari, P Nath, SM Ashraf, AN Srivastava
Dept of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University.
The study was carried at two different centres. Only 9 cases of primary malignant tumours of the renal pelvis could be collected during the period of 7 years (1984-1990). Renal pelvis malignancies constituted 0.21% of all the malignancies and 12.16% of all the malignant growths of the kidney (9 out of 74 cases). The age of these patients ranged from 24 to 70 years; the mean being 41.7 years. Male/female ratio was 8:1. Common triad of complaints (pain, haematuria and lump) was noticed in 22.2% of patients. Individually they were noticed in 77.8%, 66.7% and 44.4% of patients respectively. Transitional cell carcinoma was the commonest, seen in 7 patients (77.8%) whereas squamous cell carcinoma and adenocarcinoma were noticed in one patient (11.1%) each. Hydronephrosis, chronic pyelonephritis and nephrolithiasis were noticed in 66.7%, 44.4% and 22.2% of patients respectively. Ultrastructural study of urothelial tumours revealed tumour cells in various stages of differentiation with loss of intercellular junctions and dense collection of rough endopasmic reticulum fibrils around the nucleus.
Keywords: Adenocarcinoma, complications,epidemiology,pathology,surgery,ultrastructure,Adult, Aged, Carcinoma, Squamous Cell, complications,epidemiology,pathology,ultrastructure,Carcinoma, Transitional Cell, epidemiology,pathology,ultrastructure,Female, Hematuria, epidemiology,etiology,Human, Hydronephrosis, epidemiology,etiology,India, epidemiology,Kidney Calculi, epidemiology,etiology,Kidney Neoplasms, complications,epidemiology,pathology,surgery,ultrastructure,Kidney Pelvis, Male, Middle Age, Nephrecto
Primary malignant tumours of renal pelvis are relatively rare and constitute about 8 to 14% of all the renal malignancies,. In a large general hospital, Lomax-Smith and Seymour were only able to collect 24 cases over a period of six years. These tumours are mostly seen in adults but can also occur in pediatric age group. Pelvic tumours are detected clinically at an early stage because of early desquamation of cells and haematuria still the survival is not good enough.
The authors take this opportunity to present here the salient morphologic features of the tumours of the renal pelvis diagnosed at two major medical centres in North India.
A joint study was undertaken to review the cases of malignant growth of the renal pelvis diagnosed histopathologicaily at JN Medical College, AMU, Aligarh and KG Medical College, Lucknow, from 1984 to 1990. Besides study of clinical presentations, gross features, and microscopic details of the tumours an attempt was made to assess the ultrastructurai features of transitional cell carcinoma (TCC) of renal pelvis.
For ultrathin sections the tissue pieces were preserved in 3% glutaraldehyde. They were fixed with 1% cocodylate buffered osmium tetraoxide at 4șC for 1-2 hours. After dehydration tissue pieces were inflitrated with various combinations of durcupan ACM mixture (Fluka A.G.) and acetone. Embedding was done in gelatin capsule in ACM mixture at 60șC for 2 days. The ultrathin sections were cut by an ultramicrotome, picked up on grid and stained by uranyl acetate and lead citrate. They were examined by EM 301 Phillips Electron Microscope.
There were nine cases of malignant growths of the renal pelvis diagnosed histopathologicaHy. These patients constituted 0,018% of all the histopathological biopsies (9 out of 48840 samples), 0.21% of all the malignancies (9 out of 5639 malignant growths) and 12.16% of all malignant growths of kidney (9 out of 74 cases) diagnosed during the same period in the laboratories. The incidence of renal pelvis malignancies was 6% of all the renal malignant growths at one centre whereas it was 25% at the other. [Table - 1] (on next page) presents the salient features studied in these patients.
Age and Sex: There was a preponderance of males as the male/female ratio was 8:11. The age of these patients ranged from 24 to 70 years; mean being 41.7 years.
Clinical presentation: The duration of illness varied from 6 months to 5 years. Pain, haematuria and lump in abdomen was noticed in 77.8%,- 66.7% and 44.4% patients. Clinical triad was observed in 22.2% of patients. Clinically the diagnosis of renal cell carcinoma was made in 3 patients.
Etiological factors: Of the nine patients seven were smokers. Four of them were consuming less than 20 cigarettes/day while the other 3 smoked 20 to 30 bidies/day. None of the patients gave any specific history of taking analgesics for prolonged duration besides taking occasionally aspirin or analgin for headache or brufen for joint pains. None of them had ever worked in any rubber, aniline dye, plastic or gas industries. Nephrolithiasis was observed in two patients.
Gross features: All the patients underwent nephrectomy. The size of the kidney varied form 11x7x3 cm to 25x20x8 cm. The outer surface was smooth in 3 whereas in 6 it was irregular due to depressed scars. Cut surface revealed large, irregular, friable sessile or papillary growth filling more or less the entire pelvic space [Figure - 1].
The capsule was adherent and the corticomedullary junction was well demarcated in 3 patients. Hydronephosis was noticed in 6 patients; chronic pyelonephritis in 4 and nephrolithiasis in 2. Extension of growth into the renal parenchyma was noticed in 66.7% of patients.
Microscopic pathology. Morphologically seven patients were of urothelial type or transitional cell carcinoma (TCC) with cells arranged in papillary fashion [Figure - 2] or solid sheets showing mitoses and hyperchromatism.in 2 patients, the tumour was found to be extending to the ureter and the peripelvic tissue. Histologically the tumours were designated as grade I in 1, grad II in 4 and grade III in 2 patients.
In squamous cell carcinoma (SQCC) besides pain, the patient also complained of discharging fistula in the right lumbar region. The pelvis was filled with a nodular friable growth extending into the distended calyces. The inner surface of the calyces was ragged and filled with degenerated material.
Histologically the tumour showed sheets and groups of squamous cells with a greater variation in cell size and staining reactions, individual cell keratinisation, and a fair number of mitoses. Occassionally well formed epithelial pearls were also present. The tumour cells were infiltrating into the renal parenchyma, which revealed hyalinised glomeruli, tubules with colloid casts and mononuclear cells infiltration of the interstitial tissue. The morphological diagnosis of moderately differentiated SQCC stage III was made along with pyonephrosis, chronic pyelonephritis and nephrolithiasis.
In one patient the tumour showed the morphologic picture of well-differentiated adenocarcinoma of stage II.
Staging of the tumours was done according to Bennington and Beckwith. Of the nine patients, stage I tumour was seen in one case, stage II in 2, Stage III in 5 and stage IV in 1. It was difficult to predict any definite correlation between the grading and staging of the tumour, as the number of TCC patients was very small (7 cases only). However, it could be visualized that the higher grades corresponded to higher stages and no patients with grade III were found to exhibit stage I or II disease. Of the four patients of grade II tumour, 1 belonged to stage II and 3 to stage III. Grade I tumour belonged to stage I and was non-invasive.
Ultra-structural study of TCC of renal pelvis demonstrated groups of tumour cells in various stages of differentiation. The tumour cells were arranged in groups in close opposition to each other with minimal intercellular junctions. The junctions were less prominent or absent in undifferentiated tumours (grade III). Tumour cells showed large nuclei with scanty and irregular clumped chromatin [Figure - 3]. In a few tumour cells dense collection of rough endoplasmic reticulum (RER) fibrils was seen round the nucleus and the rest of the cytoplasm contained several mitochondria [Figure - 4].
Of the 9 patients, 3 were lost during the follow-up. The patient with SQCC survived only for 10 months. Patient with grade I TCC survived for 6 years whereas other 4 patients expired within 2 to 3 years of nephrectomy.
Tumours of the renal pelvis are extremely rare; in the present study only 9 cases of renal pelvis malignancy could be recorded during the period of 7 years at two different medical college hospitals in the country, The rarity of the lesion may further be assessed as Solanki et al from Bikaner could collect only 15 cases during a period of 23 years. Malignant tumours or renal pelvis constituted 0.21% of all the malignancies diagnosed histopathologically or 12.16% of all the renal malignancies which was in accordance to the findings of others, though a higher incidence of 20.2%, 20.4% and 23.3% have been reported by Ali and Muir, Prabhakar et al and Reddy et al respectively. On the other hand other workers ,, have reported a comparatively low incidence (7.17% to 9.7%).
These tumours were seen in the age group of 24 to 70 years with a mean age of 41.7 years - a finding compatible with that of others,, though some workers ,, have reported the average age for cases of renal pelvis malignancies as 57, 61.5, and 64 yrs respectively. Male predominance has been noticed for renal pelvis malignancy by Guha et al (61), Solanki et al  (4:1) and Ranadive et al (3.7:1). In the present study the male/female ratio was 8:1. Both the kidneys were more or less equally involved-an observation identical to that of Latham and Kay .
The chief complaints of these patients were pain (77.8%), haematuria (66.7%) and lump in abdomen (44.4%) and the triad was noticed in 22.2% of patients. Hence they may be misdiagnosed clinically as hypernephroma as was noticed in 3 patients. Wagle et al noticed haematuria in 98.7% of cases though the triad was noticed only in 19.2% of cases. Ranadive et al on the other hand noticed lump in 100% cases, haematuria in 64.3% and pain in loin in 57.1%.
There was a preponderance of TCC in the present series (77.8%) similar to the observations of others,,, whereas Prabhakar et al and Solanki et al could find squamous cell carcinoma in 100% and 66.7% of cases of renal pelvis malignancies. Nephrolithiasis was observed in 2 cases (one SQCC and one TW) whereas others,, have observed a close correlation between the renal calculi and SQCC. Other associated lesions like hydronephrosis and chronic pyelonephritis was observed in 66.7% and 44.4% cases respectively. Guha et al have reported hydronephrosis in 57.1% of the cases and nephrolithiasis in 28.5%.
The incidence of SQCC of the renal pelvis was 1.4% of all the renal malignancies in the present study, though other workers have reported it as 3.3%, to 20.4%. In this region squamous carcinoma is comparatively less common as itconstituted only 11.1% of all the renal pelvis malignancies though Sirsat  and Ranadive et al have reported the incidence as 25% and 28.5% of all the renal pelvis malignancies respectively. From one of centres included in study, only 1 case of SQCC of the renal pelvis has been reported during the period of 1965 to 1977. Generally these cases are associated with renal calculi and infection,, which are responsible for squamous metaplasia and finally to SQCC. Other factors like endogenous and exogenous chemicals, vitamin A deficiency and hormonal imbalance have been held responsible for squamous metaplasia and subsequently carcinoma,. Adenocarcinoma of the renal pelvis is extremely rare and constitutes roughly 1% of all the renal pelvis tumours,. It is presumed that the renal calculi as well as chronic infection can produce glandular metaplasia and sometimes adenocarcinoma,. Liwincz et al on the other hand, have suggested that the tumour arises as a result of epithekal cell nests and islands of mucus secreting hind gut cells persisting in the upper urinary tract.
Besides nephrolithiasis and chronic infection other factors held responsible for renal pelvic malignancies are chemical agents, excessive consumption of analgesics and cigarette smoking. None of the patients gave any history of involvement in chemical industries especially of rubber, dye and gas. Also there was no history of excessive consumption of phenacetin. TCC is more common in analgesic abusers. Such tumours are much more common in females and have a worse prognosis. Smokers are six to seven times more prone to develop a renal pelvic cancer than nonsmokers and there is a dose response relationship. Smoking could be another factor held responsible for renal pelvic malignancy as 7 patients were smokers. In Minneapolis, USA, 82% of carcinoma of the renal pelvis among males and 61% of those among females are due to cigarette smoking.
On electron microscopy urothelial tumours revealed typical features of transitional cells - superficial, intermediate and basal cells with cellular junctions but the junctions were less prominent and almost absent in undifferentiated type of carcinoma. The nuclei showed pleomorphism and there was collection of fibrils around the nuclei. The findings were in close similarity to the observations made by Tannenbaum,.
Though the number of the cases studied in the present study is small, one can conclude that the renal pelvic malignancy carried a poor prognosis, which was closely related to the grade and stage of the tumour, as higher grade tumours corresponded to higher stages. Similar observations as to grade and stage were also reported by Booth et al. Latham and Kay have reported papillary formation as a good prognostic sign and squamous differentiation or metaplasia as a bad prognostic sign. They have some doubts about the relationship of prognosis and grading of the tumours. The case with S= had a worse prognosis. The diagnosis of SQCC is usually made when the tumour is already far advanced, as symptoms in these patients could not be easily differentiated from those of calculi, infection and chronic irritation. Johansson et al  have reported 5 year survival rate as 51% in curatively operated series. Tumour grade and tumour structure exert some influence on prognosis independent of the infiltration depth. According to Porter  tumour penetration of the muscle of the renal pelvic wall, poor differentiation of the tumour and multifocal tumour formation are the main features, which adversely affect the prognosis.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4][Table - 1]