Introduction:
Renal malignancy is the 13th most common cancer worldwide.1
Approximately 90% of renal cancers are renal cell carcinomas (RCC).2 Chromophobe renal cell
carcinoma (ChRCC) is one of its rare subtypes, with an overall incidence of 5% and an equal preponderance
in both the sexes.3 Mean age at diagnosis was reported to be 53 years.4 The clear
cell RCC and the benign oncocytoma are its closest mimics on microscopy. We present this case of a
chromophobe RCC, diagnosed on routine light microscopy, owing to its relative rarity of incidence,
difficulties encountered and differential diagnoses to be considered on histopathology - as the
prognosis and management protocols differ with different variants.
Case Report:
A 70 years old diabetic, hypertensive and obese male farmer, who was also a chronic alcoholic
and beedi smoker, presented to the Surgery out-patient department of Krishna Institute of Medical Sciences,
Karad, with complaints of left-sided flank pain and passing red-coloured urine over the past six months.
The patient had no significant past, family, dietary history.
On examination, he was pale, tachypnoeic and had a blood pressure reading of 168/98 mm Hg. Abdominal
palpation revealed a small, firm to hard, non-tender lump in the left lumbar region that did not move
with respiration.
Contrast-enhanced Computed Tomography revealed a well-defined, heterogeneously-enhancing, round to oval
lesion, measuring approximately 3.7 x 3.5 x 3.5 cm at the postero- medial aspect of the left kidney. The
lesion had smooth margins and a distinct interface with the adjacent renal parenchyma and was seen
compressing the renal pelvis. There was no evidence of any infiltration into the adjacent peri-renal
structures. (Fig.1.1, Fig.1.2)
Based on these findings a provisional diagnosis of renal cell carcinoma, with a differential diagnosis
of oncocytoma was made.
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Fig. 1.1: Pre-contrast CT image of the well-defined, heterogeneously-enhancing round to oval lesion at
the postero-medial aspect of the left kidney. |
Fig. 1.2: Post-contrast CT image of the lesion showing
smooth margins and a distinct interface with the adjacent
renal parenchyma. |
Intravenous pyelography showed a large, irregular-filling defect in the left renal pelvis causing an
irregular impression on the calyces with lateral displacement of calyceal system without visualization
of the renal pelvis, which was suggestive of a neoplasm of the renal pelvis.
A pelvic ultrasonogram revealed a 9.8 x 4.5 cm sized left kidney with an iso-echoic, predominantly
solid, intra-renal mass along the mid-pole measuring 4.3 x 3.6 x 3.9 cm with few areas of cystic
degeneration and mild vascularity without local infiltration or intra-lesional calcification. The
left renal vein showed normal blood flow without thrombosis. The right kidney was essentially normal.
No other pelvic abnormalities were noted.
Routine laboratory investigations revealed a microcytic, hypochromic anaemia with a mild neutrophilic
leukocytosis and raised fasting and post-prandial blood sugar levels. Urine microscopy revealed numerous
pus cells, RBCs and red cell casts. Urine benzidine test was positive. The rest of the haematological
and biochemical investigations, including serum creatinine, protein and electrolyte levels,
were within normal limits.
A left radical nephrectomy was done and the specimen sent for histopathological examination.
On gross examination, the left kidney measured 11 x 6.5 x 3.5 cm with a nodular bulge measuring 3.4 x 2.8 cm
on the posterior aspect of the hilum. The rest of the kidney showed broad, irregular scars. On cut-section,
a well-circumscribed, grey-tan, solid tumour measuring 3.4 x 2.8 x 1.6 cm situated beneath the capsule in
the middle portion of the kidney was noted. The pelvi-calyceal system showed irregular dilatation with three
brown-black calculi. The attached ureter, artery and vein appeared uninvolved.
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Fig. 2a and 2b: Gross specimen showing the tumour arising in the middle pole near the hilum |
Microscopy of multiple Haematoxylin & Eosin-stained sections revealed renal tissue with a tumour
composed of round to polygonal cells arranged in nests, alveolar and small areas of papillary pattern.
The cells have well-defined cell-membranes, faintly eosinophilic granular cytoplasm with perinuclear clear
halos with round hyper chromatic nuclei with slightly irregular nuclear contours. Areas of necrosis are noted,
the rest of the kidney shows features of chronic pyelonephritis. The sections from the ureter, renal vein,
renal artery and perinephric fat show no evidence of tumour.
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Fig. 3a: Photomicrograph showing tumour composed of round to polygonal cells arranged in nests and alveolar
pattern.(100x, H&E). |
Fig. 3b: Photomicrograph showing cells with
well-defined cell membranes, faintly eosinophilic
granular cytoplasm with perinuclear clear halos and round hyperchromatic nuclei with
slightly irregular nuclear contours. (400x, H&E). |
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Fig. 3c: Photomicrograph showing tumour with areas of necrosis. (100x, H&E). |
Discussion:
Renal malignancy is among the most frequently occurring cancers in the Western world.1 The
incidence of renal malignancy varies geographically: incidence rates are highest in Europe, North America
and Australia; and low in India, Japan, Africa, and China, with approximately 2,71,000 new cases diagnosed
in 2008 alone.1
Renal cell carcinoma is the most common neoplasm of the kidney.2,3 It is a heterogeneous
disease, comprised of different histological variants with a distinct clinical course, genetics and response
to treatment. The 2004 World Health Organization (WHO) classification of RCC recognized several
of its subtypes. The commonest include: clear cell RCC (70%), papillary RCC (10-15%), chromophobe RCC (4-6%),
collecting duct carcinoma (about 1%) and unclassified RCC (4-5%).5
The chromophobe variant of the renal cell carcinoma was first described in 1985.6
These are diagnosed most frequently in the 6th decade of life and have an equal incidence in both sexes,
7 as against typical RCCs which show a male preponderance.8 Almost 90% of ChRCCs are
diagnosed earlier, i.e., in stage 1 or 2 of the disease. Renal vein invasion is also more uncommon - seen
only in about 5% of cases. Incidence of metastatic disease in chromophobe renal cell carcinoma is lower -
about 6-7%.9
In a summary of 28 cases, the most common metastatic sites of the ChRCC were found to be the liver (39%)
and the lungs (36%);10 while those of the RCC are the lungs (more than 50%) and bones (33%).8
Five and ten year disease-free survival rates for chromophobe RCC were 83.9% and 77.9% respectively.
The median time from nephrectomy to metastasis detection, and from metastasis detection to death were twice
as long for ChRCC than for other subtypes of RCC (i.e. papillary, clear cell RCC.7
Macroscopically, it is classically described as a solitary, circumscribed, un-encapsulated mass with a
homogeneous light brown cut surface as against the bright yellow-gray-white cut surface of the conventional
RCC. The median tumour size is 6.0 cm, which is larger than the other RCC subtypes.10
Microscopically, ChRCCs are classified into typical, eosinophilic and mixed variants depending on the
predominant cell type.11 The three types of cells described are:
- Type I (eosinophilic variant) cells are small with granular, eosinophilic cytoplasm.
- Type II (mixed variant) cells resemble the first type but are larger with a peri-nuclear, transluscent zone.
- Type III (classical variant) cells have thick, well-defined borders, wrinkled or ‘raisinoid’ nuclei and abundant,
pale, granular cytoplasm.
In this case, the tumour was composed of , round to polygonal cells with well-defined cell-membranes
arranged in nests, alveolar and small areas of papillary pattern. Individual cells had faintly eosinophilic
granular cytoplasm with perinuclear clear halos and round, hyperchromatic nuclei with slightly irregular
nuclear contours. So, a diagnosis of Mixed (Type II) chromophobe renal cell carcinoma was made.
Routine Haematoxylin & Eosin staining is generally enough to subtype renal cell carcinomas, but
differentiation between an oncocytoma, a ChRCC and a clear-cell RCC can pose occasional diagnostic dilemmas
when the tumour cells show eosinophilic cytoplasm.
ChRCCs composed predominantly of Type I cells can be mistaken for oncocytomas, owing to the small cell
size, eosinophilic granular cytoplasm and typical nested or alveolar arrangement of tumour cells. Though,
embryologically both these tumours arise from the inter-calated cells of the collecting duct system, their
prognosis differs.
The oncocytoma is a benign lesion and due to similarities in imaging and cytology findings with ChRCC,
proper pathological diagnosis of oncocytoma is primarily histopathological. The microscopic features that aid
in the differential diagnosis include - sheeting arrangement of the tumour cells, wrinkled or ‘raisinoid’
nuclei and well-defined cell borders in the ChRCC.10 Also, special staining with Hale’s colloidal
Iron will show a diffuse reticular cytoplasmic staining in the ChRCC, as against oncocytomas that exhibit a
focal positive stain confined to the luminal borders. Ancillary techniques like electron microscopy,
immunohistochemical positivity for Cytokeratin-7 (CK-7), CD-117, epithelial membrane antigen and
parvalbumin can be helpful in the diagnosis of ChRCC.10
In clear cell RCC the growth pattern is different from the ChRCC - varying from solid to trabecular
(cordlike) or tubular. Individual tumor cells in this classical RCC type are round to
polygonal with abundant clear or granular cytoplasm, which stains positive for glycogen and lipids.8
ChRCCs are often associated with a favourable prognosis, earlier stage at detection and longer survival
rates as compared with the conventional RCCs,12 hence recognition and diagnosis of this
variant by the histopathologist is important.
Conclusion:
Chromophobe carcinoma is a relatively rare variant of the Renal cell carcinoma. We present
this case on account of its relatively rare incidence. The ChRCC is a distinct entity both clinically and on histopathology. It is often difficult to distinguish on microscopy from oncocytomas and clear cell RCCs. However, as ChRCCs often show a better prognosis, an earlier stage at detection and longer survival rates as compared with conventional RCCs, recognition and diagnosis of this variant by the histopathologist is of prime importance.
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- Ljungberg B et al. The Epidemiology of Renal Cell Carcinoma. Eur Urol. Oct 2011;60(4):29-36.
- Ordonez NG, Rosai J. Urinary Tract: Kidney, Renal pelvis and Ureter; Bladder. In: Rosai and Ackerman’s Surgical Pathology. 10th ed. Vol(2). Mosby Elsevier. 2011. pp 1183-1193.
- Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma: Clinicopathological features of 50 cases. J Urol. 1995;154:964-967.
- Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Pathology and Genetics of the tumors of the urinary system and male genital organs. WHO classification of Tumours. IARC Press; Lyon, France. 2004.
- Thoenes W, Storkel S, Rumpelt MJ. Human chromophobe cell renal carcinoma. Virchows Arch Cell Pathol. 1985;48:207–217.
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- Alpers CE. The Kidney. In: Kumar V, Abbas A, Fausto N, Aster JC, eds. Robbins and Cotran Pathologic basis of disease. 8th ed. Saunders Elsevier. 2010. pp 963-967.
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- Vera-Badillo FE, Conde E, Duran I. Chromophobe renal cell carcinoma: A review of an uncommon entity. Int J Urol. May 2012:1-7.
- Akhthar M, Kardar H, Linjawi T, McClintock J, Ali MA. Chromophobe cell carcinoma of the kidney: A clinicopathologic study of 21 cases. Am J Surg Pathol. 1995;19:1245–1256.
- Onishi T, Oishi Y, Yauda S, Abe K, Hasegawa T, Maeda S. Prognostic implications of histological features in patients with chromophobe RCC. BJU Int. 2002;90:529–532.
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