• adenoma³: 
  • <5 mm. diameter⁷
  • no worse than grade 1 of 4
  • tubulopapillary pattern only⁷
• metanephric adenoma [in 1995] & adenofibroma:
• incidental finding mostly females [L06-745].
• histo: tubules & glomeruloid bodies...uniform small cells with high N/C & even chromatin
• EMA neg.
• can be confused with solid variant of papillary RCC & Wilm's.
• Imaging-detected renal cystic lesions⁴:
• Simple cysts are detectable in 25 to 30% of patients above the age of 50. The majority of renal cystic lesions are in fact simple cysts. Isolated simple cysts are benign by nature and need no further evaluation. Still, the number of patients with more complex lesions is significant, and some of these lesions will turn out to be renal cell carcinoma (RCC).

Simple cysts are reliably identified by ultrasound. Characteristics of a simple cyst include:

1. Anechoic character of the cyst;
2. Increased through transmission with posterior enhancement;
3. a sharply demarcated cyst wall.

What if the lesion does not fill the criteria for a simple cyst?
Currently the standard for further evaluation is abdominal CT with and without contrast. Bosniak (NYU) proposed a classification of renal cystic lesions based on abdominal CT findings.

Bosniak I-Thin wall, no septations, no calcifications, density 0-20, No enhancement.
Bosniak II-Same but with, few septations, and or few calcifications.
Bosniak III-Thick wall, septations, calcifications, density 0-20, No enhancement.
Bosniak IV-Thick wall, thick septations, course calcifications, density more than 20, enhancement.

The Bosniak classification translates roughly to the following:

1. We know it's a cyst
2. We're still pretty certain it's a cyst
3. We don't know what it is.
4. It's probably a tumor

More confidence can be achieved by requesting CT intervals of 5 mm rather than the standard 10mm.

• Renal cell carcinoma (RCC), clear cell:
• 70-80% of renal malignancies
• 80% of 5-10 cm. tumors are this type
• clear-cell is classical; yellow (less yellow likely higher grade), nodular gross cut surface
• IHC: LMW-ker+, vimentin positive, glycogen +
• look out for the "multilocular cystic RCC" (<10% solid component) which is essentially benign; 15% RCCs cystic.
• eosinophilic granular variant is rich in mitochondria
• cytoplasm may contain brush-border material (CD10 pos. in 94%...anti-RCC pos. in 84%) 
• tumor necrosis is a bad prognostic factor in clear cell RCC¹⁰
• sarcomatoid change in any renal tumor...biphasic malignant features...makes it a grade 4 tumor; even if completely sarcomatoid, is still a RCC⁷
• Fuhrman grade
• staging

• oncocytoma (named in 1976)⁵:
• mahogany brown cut surface color [LMC-02-6162; L07-10319].
• can reach a huge size, be multicentric, and be bilateral [LMC-05-7951].
• DDX with CRCC, below.
• often with central scar.
• can invade capsule.
• nested, alveolar or tubular growth pattern of cells with abundant eosinophilic finely¹¹ granular cytoplasm in a relatively uniform tumor⁷; should be neg. for signif. papillary or clear-cell component and neg. for necrosis.
• round nuclei with uniform chromatin & with or without prominent nucleoli¹¹.
• ck7 neg.⁹; a few CD10 pos. [maybe strongly so, LMC-05-7951] & most vimentin negative; ck 8 & ck18 & ck20 pos. & may be as a large nucleus sized cytoplasmic dot [L06-10544]; & EGFR negative.
• almost always diploid DNA; Renshaw⁷ classifies as a benign tumor.
• can have usual RCC buried in an oncocytoma or in other kidney.
• up to 32% of cases have associated ipsilaeral [LMC-05-9838 3mm papillary] or contralateral RCC¹³.

• chromophile (papillary [in 1976]) carcinoma:
• more than 95% of tumors 10mm or less in diameter are this type [LMC-02-4446; FNA-02-236; LMC-03-5023 mets ck8 pos & k903 neg; LMC-04-973; L05-1851]
• round, with beige or white cut surface, large ones having brown central necrosis (tumor necrosis is not a bad prognostic factor in papillary RCC¹⁰).
• nearly 100% CD10 pos. 
• excellent circumscription, often with a distinct fibrous capsule¹¹
• >50% papillary component and cells with non-clear cytoplasm. Predominant papillary or tubulo-papillary¹¹.
• multifocal tumors common⁷. [LMC-05-7951]
• psammoma bodies and stromal foam cells (in the gross as tiny yellow, glittery spots); cells may have scant, basophilic cytoplasm or voluminous eosinophilic granular cytoplasm⁷ 
• nuclei crowded into cell center, cytoplasm being organelle-poor except for endoplasmic reticulum, in lower grade; mitochondrial increase in higher grades
• often in chronic renal dialysis cases
• IHC: Almost 100% CD10 brush border positive⁹. Vimentin neg. & CEA faintly pos.⁶; EMA, ck7, and ck8/LMW-keratin pos. & K903 neg. (except 3% of cases...[L06-9888]).
• majority of patients with low-grade papillary RCC negative for recurrences and negative for metastases³ [LMC-05-2181]

• chromophobe-cell carcinoma [in 1985] (CRCC):
• fresh cut surface homogeneously orange and turns beige to gray-brown with formalin fixation.
• 100% 5 year survival¹¹ but it is a RCC.
• clear granular to pale granular cytoplasm (glycogen and vesicles); there is an "eosinophilic variant" quite difficult to distinguish from eosinophilic RCC¹².
• tumor necrosis is a bad prognostic factor in chromophobe-cell RCC¹⁰
• sometimes eosinophilic background with extremely distinct cell boundaries (almost like plant cells)...nuclei koilocytotic-like⁷; perinuclear halos & koilocytoid raisinoid wrinkled nuclei with coarse chromatin¹¹
• IHC: ck7 pos.⁹...84% are ck7 pos.¹². All CRCC & RCC  CD10 pos.¹²; 100%¹² of CRCC are vimentin neg.⁶; EGFR positive.
• Hale's colloidal iron stain diffusely positive cytoplasm.

• collecting-duct carcinoma [in 1986] (Bellini Tumor)⁷:
• medullary location⁵ or pelvicalyceal epicenter as a gray-white infiltrative tumor¹¹
• tubulopapillary histology & invasion incites desmoplasia & HMW-ker pos.⁵

• renal cell carcinoma with rhabdoid features⁸:
• clinically very aggressive
• histo: cells resemble rhabdomyoblasts but IHC muscle neg.
• clear, papillary, and collecting duct RCCs have had these features

• spindle and cuboidal renal cell carcinoma⁸:
• EMA pos.
• low-grade malignant
• strong assoc. with stones

• medullary carcinoma:
• only in sicklers and SC hemoglobinopathies
• central renal origin
• yolk-sac-like (&/or adenoid cystic⁵) histology; LMW-ker + and VIM -
• often lots of polys in tumor

• Pediatric (papillary & nests) RCC (ages 5-30)⁷:
• EMA weak to neg.
• usually high stage at Dx

• unclassified renal-cell carcinoma: any primary renal epithelial malignancy which does not fit one of the recognized categories (mixtures; sarcomatoid types; mucin-producing type; etc.)

• low-grade myxoid renal epithelial neoplasm with distal nephron differentiation:
very rare⁷

• mixed epithelial and stromal tumor of the kidney:
rare⁷

• small-cell carcinoma:

• mesoblastic nephroma:
• predominant tumor of 1st 3 months of life and rare after age 6 months

• Wilm's tumor:
• >80% of childhood renal tumors (age 2-4 y/o); 4% bilateral
• cut surface resembles brain
• epithelial nuclei often odd elongated, ovoid, molded or wedge shaped

• reno-calyceo-pelvic transitional-cell carcinoma:
• usual TCC: because of "field effect", one TCC at any location in the urinary tract with transitional cell lining causes clinical concern for increased risk of new tumors elsewhere. So, important to try to discern whether a cancer with squamous features arising maybe at a squamo-transitional junction is a (1) true SCC or a (2) true TCC with squamous foci or features [L07-1853].
• sarcomatoid variant: usually polypoid and micro resembles pleomorphic malig. fibrous histiocytoma (MFH) & can have focal odd stromal reactions (such as osteoclasts, osteoid, chondroid)

• angiomyolipoma:
• ordinary: HMB45 positive. [LMC-01-8368; L-05-6301]
• epithelioid angiomyolipoma: almost all in females and about 33% assoc. with tuberous sclerosis; when mostly epithelioid abnormal smooth muscle cells, the eosinophilic cytoplasm reminds of a carcinoma and they react with HMB45.

• leiomyoma of renal capsule:
HMB45 positive

• carcinoid tumor:

• cystic nephroma: mostly in women >30 y/o. well circ. by a fibrous capsule; no malig. clear cells; sometimes ovarian-like stroma

• primary renal sarcomas:

• primary renal malignant lymphoma:

References:

1. Stephen M. Bonsib, MD, of Medical College of Ga., Seminar, 21 April 2001
2. USCAP web site CME file by John N. Eble, MD (of USA), and Stephan Storkel, MD, (of Germany) 22 April 2001
3. William M. Murphy, MD consult letter23 July 2002 [LMC-02-4446]
4. Associates in Urology website newsletter
5. Ackerman's Surgical Pathology, Rosai J, 8th Ed. 1996. 
6. Haber MH, et. al., Differential Diagnosis in S. P., 2002
7. Renshaw AA, [ renal tumor review] Histopathology, 41(4):283-300, October 2002 (EBS's office)
8. Kuroiwa K, Renal Cell Carcinoma with Rhabdoid...  Histopathology 41(6):538-548, December 2002 (EBS's office).
9. Dabbs DJ, Diagnostic Immunohistochemistry, 2002.
10. Cheville JC, et. al., Comparison of Outcome & Prognostic Features..., AJSP 27:612-624, 2003. Abstract in CAP Today October 2003, p. 80.
11. Amin MB, et. al., "Prognostic impact of histologic Subtyping of Adult renal Epithelial Neoplasms", (62 cases) Am. J. Surg. Path. 26(3):281-291, 2002.
12. Abrahams NA, et. al., "Chromophobe...", Histopathology 45(6):593-602, December 2004.
13. Ackerman's Surgical Pathology, Rosai J, 9th Ed. 2004.

(posted June 2001; latest addition 7 March 2007)