Moderators: Dr. John Eble and Dr. Brett Delahunt
Section 5 -
Renal Collecting Duct Carcinoma (CDC, Bellini Carcinoma) and Related Tumors
Histological Definition of Collecting Ducts
The collecting ducts (CD) as well as the ureter, the pelvis and the calices originate from the
mesonephros. The Bellini duct, also called inner medullary CD, is the distal segment of the CD situated
in the renal medullary pyramids. For some authors it is limited to the very distal tube that opens onto
the tip of the papilla. The CD is lined by principal cells and intercalated cells. Principal cells are
cylindrocubic, eosinophilic with a cytoplasmic apical protusion into the lumen which results in a
Putative Histogenesis of Renal Epithelial Tumors
Clear cell carcinomas are supposed to originate from the proximal part of the convoluted tubule and
papillary carcinomas from the distal part. Chromophobe carcinomas and oncocytomas are supposed to
originate from the CD intercalated cells. Collecting ducts carcinomas (CDC, Bellini carcinomas) are
supposed to originate from the principal cells of the inner medullary CD.
CDC: an Evolving Concept
1955 : "Bellini epithelioma": P.Masson . Cystic tumor located in
the central region of the kidney with cysts lined by "hobnail cells" similar to the principal cells of
the Bellini ducts.
1976 : Some papillary carcinomas with hyperplastic and atypical changes
in normal adjacent collecting tubules may have a collecting duct origin (
Mancilla Jimenez 
1990 : 25 cases of CDC described in the
High grade aggressive subtype renal cell carcinoma located predominantly in the renal
medulla and pelvis, with tubular and papillary patterns containing desmoplastic inflammatory stroma.
1994 : AFIP : CDC are high grade tubular,
trabecular and papillary carcinomas or low grade carcinomas with hobnail cystic patterns.
1997 and 1998 : Amin 
and Srigley 
and UICC/WHO 1998 consensus .
CDC is a spectrum of heterogeneous renal carcinomas : from low grade through high stage and high
grade tumor (the most frequent) to renal medullary carcinoma (RMC), in patients with sickle trait disease
and sarcomatoid carcinoma.
1997 : Low grade CDC are indolent cystic tumors "13 cases of low grade
mucinous tubulocystic renal carcinoma of possible collecting duct origin" Mac Lennan .
2004 : WHO classification :
only 2 distinct categories: 1) high grade
CDC and 2) RMC.
2006 : What about the"low grade mucinous tubulocystic renal carcinoma of
possible collecting duct origin" ? They have been divided into 2 categories
This entity corresponds to the formerly Masson's Bellini epithelioma.
- a new recognized entity:" low grade mucinous tubular and spindle cell
- an emerging new entity, not recognized in the 2004 WHO classification : the tubulocystic carcinoma
: Amin 2004 and 2005 USCAP meetings
and Mc Lennan .
Collecting Duct Carcinomas (CDC) and Renal Medullary Carcinomas (RMC) : Emblematic Features
Clinical features : CDC share the same epidemiology as other renal or urothelial carcinomas:
sex ratio 2M/1F, mean age 55 years. CDC are often symptomatic (abdominal pain, nephritis colitis,
hematuria, palpable tumor, fever, loss of weight …) and present metastases at the time of diagnosis. The
most striking difference between CDC and RMC is epidemiologic : RMC are observed in young black patients
with sickle cell hemoglobinopathy disease or harboring sickle cell trait. In a large series of 40 RMC
provided by the National Wilms Tumor Study Group (NWTSG)
the patients were 5 to 32 years old (mean
14,8) and presented with high stage tumors, widespread metastases and nodal involvement.
Gross examination : Macroscopic characteristics of RMC do not differ from CDC : large grey,
white, extensive masses which infiltrate the medulla and the central part of the kidney . Hilar
structures, cortex and perinephric fat can be also involved. Some necrotic or cystic changes can be
The central location of the tumor is not really a clue for the collecting duct origin because it can
be observed in all types of renal cell carcinomas (clear cell, papillary.. ). The relation with the
urothelial pelvis is sometimes difficult to ascertain when the tumors extend along and protrude into the
renal pelvis. Some distant nodules are usually seen in the kidney as well as vascular, adrenal or
regional nodes invasion.
Microscopic features : The growth pattern displays tubular, papillary and solid
cord-like features. The stroma is quite distinctive from the stroma of other renal carcinomas: abundant
and fibrous, with important necrotic and inflammatory changes and remnants of nephron tubules and
glomeruli. The carcinomatous cells are large or medium sized cylindrocubic with eosinophilic or
basophilic cytoplasm (PAS +/-), they have a high nuclear cytoplasmic ratio and
a frequent hobnail pattern. Atypical hyperplastic changes or carcinoma in situ are classically obseved
in the adjacent collecting ducts but they are very rare and difficult to ascertain.
Ultrastructural studies demonstrated similar characteristics to principal cells of
Immunohistochemistry : The tumoral cells in CDC express EMA and diverse low and high
molecular weight keratin: CK 7, 8, 18, 19, HMWK. They may express lectins (peanuts, UEA), aquaporine 3,
racemase and vimentin
The immunoprofile of RMC is similar to CDC except the negativity of
HMWK. VEGF and HIF may be positive 
Chromosomal analysis : Karyotypes are hypodiploid with a high rate of diverse numerical and
structural aberrations, most frequently alterations of chromosome 1, 22,13 . Loss of heterozygosity
was demonstrated in 1q 32;1-32.2 and in 9p, 8p, 13q .
Among the 8 criteria proposed for the diagnosis of CDC only 3 are commonly observed*
- Anatomic situation in the medulla
- An infiltrative pattern*
- No obvious proliferation of upper urinary tract
- A papillary, tubular, solid and cystic growth pattern*
- An extensive fibrous and inflammatory stroma*
- Hobnails cells
- HMWK +, Ulex+
- The coexistence of carcinoma in situ in adjacent
Differential Diagnoses :
CDC present extensive overlaps with high grade
type 2 papillary carcinomas and with urothelial carcinomas. It remains a diagnostic challenge for
pathologists and often a diagnosis of exclusion.
| ||Medullar location ||Pyelic protusion ||Infiltrative pattern ||Papillary cystic, solid growth ||Stroma fibrous, inflammatory ||CIS in adjacent collecting tubules ||Hobnails cells|
|CDC ||+++ ||-/+ ||++ ||++ ||++ ||+/- ||+|
|RMC ||+++ ||-/+ ||++ ||++ ||++ ||+/- ||+|
|High grade papillary carcinoma ||+/- ||-/+ ||+ ||++ ||-/+ ||- ||-|
|Urothelial Carcinoma ||++/- ||+++ ||++ ||-/+ ||+ ||-/+ ||-|
| ||HMWK ||CK7 ||CK5/6 ||vimentin ||Ulex (UEA) ||Aquaporin 3 ||P504|
|CDC ||+ ||+ ||-/+ ||-/+ ||++ ||+/- ||-/+|
|RMC ||-/+ ||+ || ||-/+ ||+ ||- |
|High grade papillary carcinoma ||-/+ ||++ || ||+/- ||- ||- ||+|
|Urothelial Carcinoma ||-/+ ||+++ ||+/- ||-/+ ||++ ||+/- ||-/+|
There are increasing arguments that a subset of CDC belongs to the spectrum of urothelial carcinoma.
Collecting ducts and urothelium originate from the mesonephros. Urothelial tumor invading the kidney and
CDC invading the pelvis can share the same gross aspect. CDC is in some cases associated with an
urothelial pyelic carcinoma
Urothelial carcinoma variants can be composed of trabecular nests
and cords of cohesive cells with tubular structures producing more or less mucin, like CDC.
In a recent series of high grade carcinomas considered as CDC  most of the tumors had a
urothelial-like histological profile (UEA+, vimentin -, Aquaporine 3 +).
A molecular study on a clustering of 3583 genes in 2 RMC have also demonstrated their close relation
with urothelial carcinoma .
Most importantly, several clinical studies have recently reported the clinical benefit of treating CDC
patients with a combination of cisplatin and gemcitabine standardly used in urothelial carcinomas
- Former "Bellini epithelioma" is a low grade tubulocystic carcinoma
unrelated to a Bellini duct origin
- In the heterogeneous group of high grade renal carcinoma, two
distinct entities CDC and RMC, are still considered to be related to a Bellini duct origin. They only
differ by epidemiology (RMC occurs in young black patient with sickle trait hemoglobinopathy) and they
represent < 1% of renal cell carcinomas.
- CDC and RMC are centrally located extensive tumors of the kidney
with tubular and/or papillary patterns with an abundant fibrous inflammatory stroma.
- CDC and RMC are histologically and biologically more closely related
to urothelial carcinoma than to renal carcinoma
- CDC and RMC require the same active chemotherapy regimen as
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