Susan J. Robertson

A Comparative Study of Metastatic Renal Cell Carcinoma with Correlation to Subtype and Primary Tumor

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Oncocytic papillary renal cell carcinoma with solid architecture : Mimic of renal oncocytoma

Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non‐papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117–/PR– immunophenotype (feature shared by RCC). The CD117–/PR– ORCN also displayed α‐methylacyl‐coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

Chronic COX inhibition reduces diabetes-induced hyperfiltration, proteinuria, and renal pathological markers in 36-week B6-Ins2(Akita) mice.

Background/Aims: The widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and the sizeable impact of diabetes on the development of end-stage renal disease substantiate the need to determine their effect on the evolution of diabetic nephropathy (DN). We hypothesized that chronic ibuprofen and NS-398 will differentially affect many aspects of DN in B6-Ins2Akita mice, including glomerular filtration rate (GFR), growth, and fibrosis. Methods: B6-Ins2Akita and wild-type mice were separated into six groups. At 20 weeks of age, NSAIDs (1 mg/kg/day) were added to the drinking water daily. At 36 weeks indicators of renal function and DN were examined. Results:Urinary PGE2, PGEM, TXB2, and 6-keto-PGF1α were increased in diabetics, and reduced by NSAIDs. Regional differences in cyclooxygenases were observed. Diabetics displayed hyperglycemia, albuminuria, and increased kidney/body weights, glomerular diameters, and FITC-inulin clearance. NSAIDs did not affect growth, but albuminuria and FITC-inulin clearance were reduced. Also, p27 and fibronectin were increased in diabetics and attenuated by ibuprofen. Conclusion: NSAIDs reduced diabetic change: GFR, albuminuria, p27, and fibronectin. The effects of ibuprofen are similar if not more beneficial than COX-2 inhibition by NS-398. This study has clinical relevance for diabetics prior to overt nephropathy. Future studies should reveal the effects of NSAIDs in a more severe disease environment.

Renal cell carcinoma with mixed features of papillary and clear cell cytomorphology: a fluorescent in situ hybridization study

We performed fluorescent in situ hybridization (FISH) to investigate the numeric change of chromosomes 7, 17, and Y and loss of chromosome 3p in “papillary renal cell carcinomas (RCC) with extensive clear cell changes (CCC).” Consecutive cases of RCC over a 12-year period were reviewed to identify “papillary RCC with extensive CCC.” Immunostaining for cytokeratin 7 and alpha-methylacyl-CoA racemase (AMACR) and FISH for chromosomes 7, 17, Y, and 3p were applied. Of the total of 521 RCC retrieved, there were 49 RCC with papillary architecture and clear cell areas that could be divided into: Group 1 (12 cases), typical clear cell RCC with focal areas of papillary formation; Group 2 (28 cases), focal typical papillary RCC having papillary architecture with extensive CCC; and Group 3 (nine cases), RCC with an admixture of eosinophilic/clear cytoplasm and solid/papillary architecture. Group 1 showed negative immunoreactivity for CK7 and AMACR and absence of numeric chromosomal gain or loss of chromosomes 7/17 and Y. Groups 2 and 3 showed variable reactivity for CK7 and AMACR. Tumors in group 2 and five in group 3 showed trisomies of chromosomes 7 and/or 17 with or without loss of chromosome Y. Loss of small arm 3p was observed in groups 1 and 3 but not in group 2 tumors. In conclusion, papillary RCC may show phenotypical CCC mimicking clear cell RCC. In a small number of cases with mixed histopathological features, FISH is helpful in subtyping RCC.

Composite renal cell carcinoma and angiomyolipoma: a study of the histogenetic relationship of the two lesions.

The purpose of the present study was to investigate the possible histogenetic relationship of renal cell carcinoma (RCC) and angiomyolipoma (AMYL) occurring in the same renal nodule by examining two cases of composite RCC and AMYL in patients without stigmata of tuberous sclerosis and by reviewing the medical literature of similar cases. Case 1 represents an epithelioid variant of AMYL with multiple additional nodules of typical AMYL in a surgically removed kidney. The patient subsequently developed a lesion consisting of a mixture of epithelioid variant of AMYL and RCC 24 months later in the retroperitoneum and, an additional 4 months later, in the liver. The RCC cells resembled mononucleated epithelioid cells of the epithelioid AMYL except that they were focally reactive with epithelial membrane antigen (EMA) in the retroperitoneum and focally reactive with both EMA and cytokeratin (CK) in the liver. Case 2 consisted of a typical AMYL admixed with a chromophil cell RCC. A review of the medical literature revealed seven additional cases with histopathological findings similar to this case. All cases had multiple foci of typical AMYL. Immunostaining results are available in five tumors. Chromophil RCC showed variable reactivity with CK and EMA. In addition, RCC in the two cases in the present study also displayed a positive reaction with mucin staining and a positive reactivity with carcinoembryonic antigen. There appears to be a spectrum of histopathological and immunohistochemical changes from the epithelioid variant of AMYL through a mixed epithelioid AMYL/RCC to chromophil RCC in three successive specimens in case 1. Moreover, the intimate admixture of AMYL and RCC and the similar expression of epithelial markers of RCC in the two cases in the present study, as well as other cases in the literature, suggest that some RCC develop from the same precursor cell as AMYL or from a component of AMYL.

Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity

Aims: Clear cell renal cell carcinoma (CRCC) with diffuse immunoreactivity for CK7 is described. Methods: All cases of CRCC, measuring 20 mm or less in diameter over a period of 10 years, were examined. Areas of regenerative epithelial cell nests (REC) were also examined. Results: Fifteen specimens containing 29 nodules were diagnosed as CRCC due to the characteristic clear cytoplasm. Of these 29 nodules, 21 showed diffuse CK7 positivity while eight showed CK7 negativity. The CK7 positive CRCC measured less than 16 mm and contained varying proportions of tumour cells with chromophil cytoplasm. Architecturally, CK7 positive CRCC consisted of cysts and solid cell nests with tubulo‐acinar formations or papillary formations. Immunostaining for AMACR, CD10 and RCC showed negative or focal reactivity in the CK7 positive CRCC, frequently positive reactivity in CK7 negative CRCC and negative reactivity in REC which also displayed strong CK7 reactivity. The ten patients with 21 CK7 positive CRCC developed no metastatic disease over a follow up time that ranged from 1 to 10 years (mean of 3 years). Conclusions: CRCC characterised by diffuse CK7 positivity represents a distinct type of CRCC with characteristic histopathological and immunohistochemical features.

Diagnosis of Renal Malacoplakia by Fine Needle Aspiration Cytology

BACKGROUND Malacoplakia is a rare chronic inflammatory disease first described by von Hansemann in 1901. L. Michaelis and M. Gutmann published the first report in 1902, describing the characteristic round intracellular and extracellular inclusions, or Michaelis-Gutmann bodies. Renal malacoplakia is a form of chronic tubulointerstitial nephritis the clinical and radiologic findings of which are often suggestive of a neoplasm. Renal malacoplakia may be related to megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis. CASE A 67-year-old male presented with acute left loin pain suggestive of uretery colic. The past medical history was unremarkable and physical examination within normal limits. Renal ultrasound and computed tomography showed a 3.5-cm, cystic mass with a thickened, irregular wall located centrally within the left renal sinus. The size of the left kidney was 11.5 cm. A renal arteriogram provided no evidence of a vascular mass of any type. Fine needle aspiration (FNA) revealed many large, foamy, granular macrophages with large, eccentric nuclei and prominent nucleoli containing round inclusions that exhibited a laminated appearance, consistent with the structure of Michaelis-Gutmann bodies. Many were also present extracellularly. CONCLUSION To our knowledge this is the first case of renal malacoplakia diagnosed by fine needle aspiration. This case demonstrates the value of FNA in determining the nature of a radiologically nonspecific lesion. It highlights the value of FNA as a substitute for or preliminary method before more invasive procedures in the diagnosis of a treatable disease entity.

Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma

Aims:  To investigate the reactivity for oestrogen and progesterone receptors (ER and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC).

Primary prostatic central zone adenocarcinoma

The central zone (CZ) of the prostate is embryologically, anatomically, and histologically distinct. High-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma (PAC) are encountered in the CZ, but have not been well studied. Non-CZ PAC that spread into the CZ can mimic CZ PAC. We reviewed 300 consecutive radical prostatectomies performed for PAC to identify cases showing PAC and HGPIN in the CZ. There were nine PAC (3%) localized predominantly in the CZ, presenting as a single tumor nodule (8/9) and associated with 4.5+/-1.1 foci HGPIN in the CZ and with only 1.7+/-0.5 foci in the PZ. Of the 291 non-CZ PAC, 24 cases showed satellite tumor nodules in the CZ, and 92 cases demonstrated secondary contiguous spread to the CZ. As compared to the non-CZ PAC, CZ PAC tended to have lower tumor volume, but had higher Gleason scores (8.10+/-0.6 vs. 6.30+/-0.7, p<0.05), as well as a higher incidence of a ductal carcinoma component (6/9), higher rates of capsular penetration, positive resection margins (4/9), and seminal vesicle spread (2/9). The CZ HGPIN associated with CZ PAC demonstrated cells with prominent nucleoli and formed either slender papillary structures or cribriform/solid patterns. The correlating positive biopsy cores were from the mid portion or from base of prostate and contained foci of HGPIN in 4/7 cases. The CZ PAC is characteristically accompanied by more foci of HGPIN in the CZ than in non-CZ and is associated with high grade and high stage. Preoperative diagnosis of CZ PAC can be suspected due to the histopathological features in the biopsy and is important to improve the free surgical resection rate.

Oncocytic renal cell carcinoma with immunohistochemical properties of renal oncocytoma

Renal oncocytoma (RO) is a characteristic benign renal tumor. The existence of malignant RO is controversial and anecdotal, partly due to a lack of specific markers for RO. With recent advances in immunohistochemistry, RO can be distinguished from other renal neoplasms with routine stains and with the aid of immunostaining. We report two cases of renal neoplasms with similar histopathological appearances. They were characterized by oncocytic cytoplasm, numerous intra-cytoplasmic vacuoles, uniform round to oval hyperchromatic nuclei with remarkably thick nuclear membranes and prominent nucleoli. The tumor cells were closely packed and disposed in an alveolar pattern. The neoplastic cells were diffusely reactive for CD117 and progesterone receptor, and diffusely or focally reactive for cytokeratin AE1/AE3, and focally reactive for cytokeratin 7, CD10, and racemase. The cells were non-reactive for renal cell carcinoma (RCC) antigen, vimentin, S100, and neuroendocrine markers. One tumor showed lymph node metastasis. Due to the remarkable cytological atypia, lymph node metastasis, and similar immunological features of RO, these two tumors likely represent a distinct subtype of RCC related to RO.