Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

肾嫌色细胞癌和嗜酸细胞腺瘤的形态学、组织化学和免疫表型的比较研究

目的探讨肾嫌色细胞癌（ehromophobe renal cell carcinoma,CRCC）和嗜酸细胞腺瘤（oncocytoma）的临床病理学特征、诊断和鉴别诊断。方法对手术切除的13例肾嫌色细胞癌和6例肾嗜酸细胞腺瘤进行眼观、光镜和电镜观察,Hale胶体铁和免疫组化染色。结果嫌色细胞癌以实体结构为主,胞质半透明或嗜酸颗粒状,核皱缩,有核周空晕;其中6例（46％）为嫌色细胞癌嗜酸变型;电镜下见胞质内微泡和管泡状嵴线粒体;Hale胶体铁染色12／13阳性。嗜酸细胞腺瘤以巢状结构为主,胞质嗜酸颗粒状,核圆伴小核仁;1例（16．7％）出现核异型性;电镜下见胞质内层状嵴线粒体;Hale胶体铁染色阴性。免疫组化两者均表达E—cadhefin、EMA,不表达CD10、CK20、vimentin;CK7在10／13例嫌色细胞癌中呈强阳性表达,2／6例嗜酸细胞腺瘤呈灶性表达。结论肾嫌色细胞癌和嗜酸细胞腺瘤形态学各有特征,免疫表型相似,鉴别诊断基于生长方式和细胞学特征,Hale胶体铁染色和电镜检查是区分二者的有效手段。     

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.     

Chromophobe renal cell carcinoma with calcification: Report of a case with rare finding on aspiration smears

Chromophobe renal cell carcinoma (ChRCC) is a distinct variant of renal cell carcinoma. It is important to identify this entity because it has a significantly better prognosis than clear cell (conventional) renal cell carcinoma. We report the case of a 56-year-old male who presented with 10 days history of painless hematuria. There was no palpable swelling or systemic symptoms. On radiological examination the possibility of a right renal neoplasm was considered. Ultrasound guided aspiration was done and cytological features of ChRCC were noted. In addition, numerous foci of calcification were seen, which was an unusual cytological feature for ChRCC. The characteristic cytomorphology of ChRCC makes it possible to render a preoperative diagnosis on fine needle aspiration cytology (FNAC). We report the case to emphasize the importance and possibility of diagnosing of ChRCC on cytology. In addition, the extensive calcification as seen in our case is an unusual cytological finding not previously reported in cytology smears.     

Chromophobe cell renal carcinoma and its variants--a report on 32 cases

This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical investigations on the intermediate filaments show a positive reaction for cytokeratins No. 18 (uniformly) and Nos. 7 and 19 (to varying extents) for both variants, whereas vimentin was not found in any of these carcinomas, in contrast to the clear-cell type. The cytomorphological grading revealed predominantly G II tumours. A lymph node metastasis was found in one patient. On the basis of the mortality curves determined, the prognosis for patients with chromophobe cell carcinomas is more favourable than that of the clear-cell type. In terms of differential diagnosis, on the one hand, the typical (light) variant of the chromophobe cell RCC must be delimited from the clear-cell RCC, and on the other hand, the eosinophilic variant must be distinguished from the chromophilic or 'granular' RCC. Microscopic, histological, histochemical, electron microscopic, and intermediate filament analysis results document that the chromophobe cell type of RCC is a distinct entity. The implications for the nomenclature of RCC, especially with regard to the 'granular' type, are discussed.     

Synchronous chromophobe and papillary renal cell carcinoma. First report and review of the pathogenesis theories

The coexistence of different subtypes of renal cell carcinoma (RCC) within a single kidney is an extremely unusual entity. Presented herein is the case of a 57-year-old man with two RCC of chromophobe and papillary histology. Very few reports in the literature describe double or triple synchronous renal neoplasms. To our knowledge this is the first report of this RCC subtype combination, which might trigger further investigation on the RCC pathogenesis theories.     

Chromophobe renal cell carcinoma with neuroendocrine differentiation

Chromophobe renal cell carcinoma was described by Thoenes et al. in 1986, and associations with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma have been described. We report a case of chromophobe renal cell carcinoma which showed neuroendocrine differentiation. This is the first known case to be clearly identified as such. The patient was a 56‐year‐old man with constant right flank pain and hematuria; CT scan revealed an 8.5 cm non‐homogeneous mass involving the right kidney. Right radical nephrectomy was performed. The tumor showed a mixture of classical and eosinophilic patterns of chromophobe cell carcinoma. Additionally, it showed insular, glandular and rosetoid‐like formations embedded in a dense eosinophilic hyaline stroma. The cells were cuboid or cylindrical with well‐defined boundaries, finely stippled chromatin and a small nucleolus. The appearance of the cytoplasm varied from faintly eosinophilic to coarsely granular eosinophilic. Immunohistochemically, the neuroendocrine areas were reactive for C‐kit, epithelial membrane antigen, cytokeratin, cytokeratin 7, chromogranin A, neuron‐specific enolase, CD56 and S‐100 protein. Our case represents a typical chromophobe carcinoma with neuroendocrine differentiation. Additionally, the immunohistochemical profile in both types of lesion suggests a common origin from renal tubular cells.     

Oncocytic renal cell carcinoma having papillotubular growth: rare morphological variant of papillary renal cell carcinoma

Herein is described a unique renal cell tumor with previously unreported morphological and immunohistochemical features. The patient was a 78-year-old Japanese man. A huge left renal tumor was found on ultrasound during evaluation of left abdominal distention. The tumor was macroscopically characterized by a non-infiltrative border, pale yellow to grayish color, foci of hemorrhage and partial edematous change. Histologically the tumor had an extensive small tubular growth pattern often with papillary fronds mainly composed of oncocytic cells with deeply eosinophilic granular cytoplasm. Clear vacuolated cells were scattered among the oncocytic cells. The present case had an unusual immunohistochemical profile for all known types of renal cell tumors, but both the oncocytic cells and the clear vacuolated cells were strongly immunoreactive for α-methylacyl-coenzyme A racemase. It is concluded that the tumor may be a candidate for a rare variant of papillary renal cell carcinoma. Further cases having similar features are awaited for a definitive classification of this tumor as a previously undescribed tumor type.     

Renal papillary adenoma--a putative precursor of papillary renal cell carcinoma

The precursor lesions of renal cell carcinoma (RCC) are unknown. The purpose of this study is to determine the incidence, histomorphological features, and immunohistochemical features of papillary adenoma and elucidate its potential relationship to RCC. We reviewed 542 consecutive nephrectomy specimens over an 8-year period. Immunohistochemistry was carried out with antibodies specific for alpha-methyl-coenzyme A racemase (AMACR) and glutathione S-transferase alpha (clear-cell RCC marker). Thirty-eight (7%) nephrectomy specimens showed histologic evidence of papillary adenoma. Of these 38 cases, 18 (47%) arose in the setting of papillary RCC (PRCC). Seven papillary adenomas (18%) occurred in the setting of acquired polycystic kidney disease (APKD), 6 in clear-cell RCCs, 3 in chromophobe RCCs, 2 in end-stage kidney disease, 1 in oncocytoma, 1 in angiomyolipoma, and 1 in renal schwannoma. Furthermore, papillary adenomas were more commonly found in kidneys removed for PRCC (25%, 18/71) than in kidneys harboring clear-cell RCC (1.9%, 6/318). Histomorphologically, papillary adenomas were characterized by varying proportions of papillae and tubules formed by cuboidal cells with scant basophilic cytoplasm similar to those in type 1 PRCC. Adenomas associated with PRCC tend to be multiple in number (61% [11/18] of cases had >2 adenomas; mean, 5). In contrast, 100% of papillary adenomas arising in other conditions had less than 2 adenomas. Most of the adenomas (82%, 31/38) stained strongly for AMACR in a fashion similar to that of PRCC. The 7 AMACR-negative cases all arose in the setting of APKD. In this study of surgical specimens, the high coincidence, multifocality, and histologic and immunohistochemical similarities between papillary adenoma and PRCC suggest that the 2 are strongly associated and may represent a continuum of 1 biologic process. In contrast, adenomas associated with APKD exhibit distinct morphological and immunohistochemical features and, therefore, may have an entirely different pathogenesis.     

A case of a novel entity: eosinophilic solid and cystic renal cell carcinoma

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a relatively newly described entity characterized by specific morphological features and a consistent immunohistochemical profile. The vast majority of cases are sporadic, but tumours with identical histological appearances have been reported in patients with tuberous sclerosis complex (TSC). The distinction between a sporadic or syndrome associated ESC-RCC is not possible without, at a minimum, exploring the patient's clinical context and family history. We present a case of a young female patient who presented with bilateral renal tumours, one of which has been diagnosed as ESC-RCC, and is awaiting genetic testing to exclude underlying TSC.     

Clear cell papillary renal cell carcinoma: a review

The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type.     

Chromophobe renal cell carcinoma with liposarcomatous dedifferentiation - report of a unique case

Sarcomatous transformation of chromophobe renal cell carcinoma (CRCC) is a well recognized phenomenon. Of the published cases with sarcomatous transformation of CRCC, none have shown liposarcomatous differentiation. Out of a cohort of 250 cases of CRCC, 19 (7.6%) showed sarcomatous differentiation. In one case (female, age 46 years), the sarcomatous component of the tumor displayed histological features of a pleomorphic liposar-coma. Light microscopic examination revealed a biphasic pattern with a chromophobe renal cell carcinoma(CRCC) and a high-grade sarcomatous component containing large pleomorphic lipoblasts. In several areas both components were intermingled. The conventional CRCC component showed classic histological features with calcifications, medium-sized polygonal cells arranged in solid-alveolar structures with raisinoid nuclei, pale-eosinophilic flocculent cytoplasm with perinuclear haloes. In addition, a microcystic-adenomatous component had luminal spaces filled with erythrocytes. The CRCC was positive with Hale''s colloidal iron-stain whereas the sarcomatous component was negative. The CRCC component was diffusely positive for cytokeratin 7, parvalbumin and racemase but negative for cy-tokeratin 20, vimentin, CD10, carboanhydrase IX and S100-protein. The pleomorphic liposarcomatous component displayed immunereactivity for CD10, vimentin, racemase and focally for carboanhydrase IX. The proliferative activity (Mib-1/Ki-67) was 5% in the CRCC and 30% in the pleomorphic liposarcomatous component. No immunereactivity for MDM2 or CDK4 was detected.This is the first reported case of a sarcomatoid CRCC where the sarcomatous component displayed features of a pleomorphic liposarcoma. The patient died from widespread metastatic disease 12 months after nephrectomy.     

Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray

AIMS: In some cases distinction between chromophobe renal cell carcinoma (CRCC), oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic variant) using routine light microscopy remains problematic. The present study investigates the level of agreement in the diagnosis of CRCC, as well as the histological features most frequently used for this diagnosis by two pathologists with a special interest in renal neoplasia. The sensitivity and specificity of immunohistochemical markers in cases with overlapping histological features in the diagnosis of CRCC were also studied. Electron microscopy was performed, as a diagnostic gold standard, on all of the cases. METHODS AND RESULTS: Thirty-two renal tumours with predominantly eosinophilic cytoplasm were reviewed in a blinded fashion by two pathologists. The diagnosis and morphological features used to render each diagnosis were tabulated. Validation of the utility of keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin, RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed by the construction of a tissue microarray (TMA) master block. Based on histological criteria alone, overall agreement on the diagnosis of these tumours was reached in 69% of the cases, while there was total disagreement in 12%. In 59% of the cases, total agreement was reached in classifying the case as a CRCC based on histology alone. Kappa statistics for interobserver variability were calculated as only slight agreement (kappa = 0.3). The histological features most frequently associated with a diagnosis of CRCC were accentuated cell borders (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear halos (74%). The most sensitive and specific marker for CRCC was parvalbumin (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/ vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4). CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC. Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC. Hale's colloidal iron and the RCC antigen marker were not contributory. Finally, the antimitochondrial antibody was found to be fairly sensitive (0.83) for excluding CRCC. CONCLUSIONS: A small but significant proportion of renal tumours with cells having eosinophilic cytoplasm cannot be classified, even by experienced pathologists, based on histology alone. In these cases it is imperative to use markers with known sensitivity and specificity for the diagnosis of CRCC.     

Chromophobe renal cell carcinoma with osseous metaplasia containing fatty bone marrow element: a case report

A 27-year-old woman presenting with epigastric pain and dyspepsia was found to have a calcified mass in the upper-middle right kidney. Gross examination of the nephrectomy specimen revealed a 6.5 x 5 x 4 cm renal tumor with dense calcification and ossification. Histopathological examination of the tumor showed solid, trabecular sheets and nesting of polygonal epithelial cells with abundant cytoplasm and prominent cell border and mature bony tissue enclosing fatty marrow. Renal cell carcinoma is frequently associated with calcification, but ossification is extremely rare. To our knowledge, we report the fourth case of a chromophobe renal cell carcinoma with extensive calcification and ossification.     

Primary renal glomus tumor with concurrent papillary renal cell carcinoma and multiple papillary adenomas in a patient with end stage renal disease: a case report and clinicopathologic analysis

Glomus tumors are mesenchymal tumors commonly seen in the extremities, and rarely seen in deep visceral organs. This is due to the lack of glomus bodies in visceral organs. Here, we describe an unusual association between glomus tumor and co-existing papillary renal cell carcinoma, multiple papillary adenomas, and end stage renal disease. We discuss our diagnostic approach and differential diagnoses, along with an extensive review of all reported benign and malignant primary glomus tumors. A 63-year-old male with a known history of a kidney transplant, end-stage renal disease, and previous nephrectomy of his right kidney due to a renal mass (papillary renal cell carcinoma) presented with a renal mass. Microscopic examination showed papillary carcinoma, multiple papillary adenomas, and a small nodule with uniform, round to oval cells. Immunohistochemical work-up revealed the small nodule to be a glomus tumor. Only 28 cases of primary renal glomus tumors have been reported in the literature. Most were discovered incidentally. None of the reported cases have occurred along with other renal tumors. This is the first case of the unusual combination of primary renal glomus tumor arising in the native kidney of a renal transplant patient with concurrent papillary renal cell carcinoma and multiple papillary adenomas (renal adenomatosis). We also explore the possible genetic basis behind this association.     

Huge renal cyst with parietal renal cell carcinoma,osseous metaplasia and a papillary adenoma: a case report with unique clinicopathological features and literature review

The unique clinicopathological features of a giant solitary renal cyst with a parietal clear cell carcinoma in contiguity with a focus of osseous metaplasia and a papillary adenoma are reported. Ultrasonography and computed tomography showed a single cyst with a focal wall irregularity. During surgery, a frozen section revealed the presence of a renal cell carcinoma of clear cell type, so a nephrectomy was performed. After extensive pathological sampling of the cyst's wall, a focus of osseous metaplasia in contiguity with the main tumour and a microscopic papillary adenoma were found. Diagnostic implications for the present case are discussed within a pertinent literature review.     

LMP2, a novel immunohistochemical marker to distinguish renal oncocytoma from the eosinophilic variant of chromophobe renal cell carcinoma

LMP2 is a subunit of the immunoproteasome that is overexpressed in oncocytic lesions of the thyroid gland. This study was designed to assess the expression profile and diagnostic utility of LMP2 in two renal oncocytic tumors that share similar morphologic features but have different clinical outcomes: renal oncocytoma (RO) and the eosinophilic variant of chromophobe renal cell carcinoma (CHRCC-EO). A total of 56 RO, 38 classic CHRCC, and 7 CHRCC-EO cases, as well 84 normal kidney controls, were selected from the Johns Hopkins surgical pathology archive and stained for LMP2 using a standard immunohistochemical protocol. Sections were scored for cellular location (nuclear versus cytosolic), intensity (from 0 to 3), and percent of area involved (from 0 to 100%), and an H score was calculated multiplying the intensity by the extent of the staining signal. The cytoplasmic expression of LMP2 was similar among the renal lesions, being present in 44 of 56 (79%) ROs, 27 of 38 (71%) CHRCCs, and 7 of 7 (100%) CHRCC-EO cases. The nuclear expression of LMP2, however, was more informative. All CHRCC-EO cases (7 of 7, 100%) strongly showed nuclear LMP2 staining, as opposed to only 2 of 56 (4%, P < 0.0001) ROs and 9 of 38 (24%, P = 0.0001) classic CHRCCs. These results suggest that the nuclear LMP2 expression can be used in clinical scenarios where histological distinction between RO and CHRCC-EO remains challenging.