SECTION I. GENERAL CONSIDERATIONS

E. Immunohistochemistry



  1. Clear cell renal cell carcinoma
    The main characteristic of clear cell RCC is the coexpression of cytokeratins (CK 8/18, 19, 7) and vimentin. Dedifferentiation leads to an increasing expression of vimentin and finally disappearance of keratins on the immunohistologic level. The perimembranous positivity changes to a perinuclear (centroplasmic) positivity. The presence of brush border-associated antigens like villin, CD 10 and CD 13 supports the proposed histogenetic development from the proximal tubule. A kidney specific gamma GT antibody, which can be applied on paraffin sections, is helpful in differential diagnosis of metastatic clear cell, carcinoma of unknown primary as it proves the renal origin.

  2. Chromophil renal cell carcinoma
    Chromophil RCC have an immunohistologic profile similar to clear cell RCC. The vimentin expression can be very weak overall but pronounced at the basal cell pole in the highly differentiated basophilic cell types. Lectins like DBA and SBA are found in chromophil RCC but not in clear cell RCC. Mab RCC 38 selectively reacts with chromophil RCC and can serve as a marker for this special kidney tumor type. The common antigen characteristics are a strong argument for the close relationship between clear cell and chromophil RCC and their origin from the proximal tubule.

  3. Renal Oncocytoma
    As a rule oncocytomas do not express vimentin, but in central regressive areas they can show focal vimentin positivity. They also lack antigens of the proximal tubule and are positive for antigens of the collecting duct, especially those of the intercalated cells like carbonic anhydrase C and H+ ATPase. The band 3 anion carrier protein found in type a intercalated cells can be detected only in oncocytomas, consistent with origin in the collecting duct. While CD 44s can be found on the cell surface, CD 44v6 is totally absent.

  4. Chromophobe renal cell carcinoma
    Chromophobe RCC are strongly positive for cytokeratin 8/18 and often for CK 7 but weakly positive for CK 19 and negative for vimentin. They share the positivity for carbonic anhydrase C and some lectins like DBA, SBA, and WGA with oncocytomas but lack band 3 anion carrier positivity. Another distinctive feature is the coexpression of CD 44s and CD44v6 on the cell membrane, which is of differential diagnostic importance.

  5. Collecting duct carcinoma
    Collecting duct carcinomas may coexpress cytokeratins (CK 8/18) and vimentin. They show pronounced cytoplasmic positivity for CK 19 and UEA-1 but lack CK 13, antigens of the proximal tubule and of the intercalated cells. Their columnar epithelial differentiation is reminiscent of the principal cells of the medullary collecting duct.

  6. Urothelial carcinoma
    The immunohistological profile of intrarenal urothelial carcinoma differs totally from those mentioned above. They express cytokeratins typical of both columnar epithelium(CK 8/18, 19, 7, and 20) and squamous epithelium(CK 5/14/17, and 13) and lack vimentin. Thus immunohistology favors histogenesis from urothelial cells within the ducts of Bellini.

  7. Neuroendocrine tumors of the kidney
    The neuroendocrine tumors of the kidney lack vimentin and squamous cell-specific cytokeratins. They are positive for columnar epithelial cytokeratins (CK 8/18, and 19), and depending on a prevailing endocrine or neurogenic differentiation, may be positive for chromogranin, synaptophysin, and neurofilaments. These antigens cannot be detected in any other RCC.

  8. Metanephic adenoma
    In solid tumor areas, the tumor cells express vimentin only whereas in more differentiated tubular or glomeruloid areas some cytokeratins can be found but not CK 19. Lack of NCAM is of importance for the differential diagnosis of nephroblastoma.

    Summing up the data, there is immunohistological diversity among the renal cell neoplasms. The immunohistological differences reflect the different histogenesis of the tumors and point to histogenetic relationships in case of common findings (clear cell RCC and chromophil RCC, oncocytomas and chromophobe RCC).

Tumor Type C
K
8
&
1
8
C
K
1
3
C
K
1
9
V
I
M
E
N
T
I
N
U
E
A
1
C
D
3
4
D
E
S
M
I
N
A
C
T
I
N
H
M
B
4
5
N
S
E
&
S
1
0
0
C
H
R
O
M
O
G
R
A
N
I
N
N
C
A
M
C
L
A
Clear cell RCC +-+/-+---------
Chromophil RCC +-+/-+---------
Renal oncocytoma +-+/-----------
Chromophobe RCC +-+/--+--------
Collecting duct carcinoma +-++/-+--------
Neuroendocrine tumors +--------++--
Metanephric adenoma +/---+---------
Wilms' tumor +/---+--+/-+/--+/--+-
Leomyoma/leiomyosarcoma +/---+--++-----
Rhabdomyosarcoma +/---+--+--+/----
Hemangioma/angiosarcoma +/---+++-------
Hemangiopericytoma ---+---------
Angiomyolipoma +/---+-+/-+/-+++/----
Lipoma/liposarcoma ---+-----+---
Malignant fibrous histiocytoma+/---+-+++-----
Malignant lymphoma ---+-+/-------+
CK=cytokeratin, UEA1=Ulex europaeus lectin