CA9 level in renal cyst fluid: a possible molecular diagnosis of malignant tumours

Aims:  The preoperative differentiation of malignant renal cystic tumours from benign lesions is critical, and it remains a common diagnostic problem. The aim was to examine if the Carbonic anhydrase 9 (CA9) level in cyst fluid can provide a molecular diagnosis of malignant cyst.
Methods and results:  Twenty-eight patients with a cystic renal mass were included. Fine-needle aspiration was performed to obtain the fluid. Postoperative pathology confirmed that there were 16 cystic renal cell carcinomas. Twelve benign cystic tumours were used as controls. One hundred microlitres of supernatant of cyst fluid was used to measure the CA9 protein level, which was measured by an enzyme-linked immunosorbent assay technique. CA9 was strongly detected and considered as positive in the cyst fluid of all 16 cystic malignant tumours (>1000 pg/ml), whereas its expression was negative in 11/12 benign cystic tumours (<300 pg/ml). The difference in percentages of positive CA9 between malignant and benign renal cystic tumours was significant ( P  < 0.001).
Conclusion:  The fluid of malignant cystic renal tumours contains a high level of CA9 protein. The measurement of CA9 level in cyst fluid may be used as a molecular diagnosis for differentiation between malignant and benign renal cystic masses.     

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: the importance of tumor size

PURPOSE: The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. MATERIALS AND METHODS: Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. RESULTS: Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those < or = 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors classed as stage > or = T3 was significantly less among tumors < or = 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrman's nuclear grades > or = 3 was also significantly less among tumors < or = 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrman's nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. CONCLUSION: In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrman's nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.     

Acquired cystic disease‐associated renal cell carcinoma is the most common subtype in long‐term dialyzed patients: Central pathology results according to the 2016 WHO classification in a multi‐institutional study

New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with end‐stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)‐associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD‐associated RCC. ACD‐associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD‐associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD‐associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD‐associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD‐associated RCC.     

Spindle and cuboidal renal cell carcinoma,a tumour having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/ spindle and cuboidal renal cell carcinoma components

AIMS: We present the largest series of an unclassified subtype of renal cell carcinoma, which seems to be a distinct morphological entity and which is sometimes designated as spindle and cuboidal renal cell carcinoma. METHODS AND RESULTS: Eleven cases of spindle and cuboidal renal cell carcinoma were found among 7000 primary renal cell tumours in Pilsen's routine and consultation files. The patients were five men and six women. They ranged in age from 22 to 65 years (mean 56.8). Microscopically, the tumours were composed of two main populations of cells. First, the preponderant type of cells was formed by flattened, spindle cells with sparse cytoplasm. The second cell type was a small cuboidal cell with clear to light eosinophilic cytoplasm. Spindle-shaped cells were arranged in a fascicular pattern often reminiscent of low-grade smooth muscle tumours. Solid areas of spindle cells were also present. Small cuboidal cells formed sparse tubular structures lined by a row of single cells. In addition to all previous published cases of spindle and cuboidal renal cell carcinoma we observed an association of nephrolithiasis in our cases. It was seen in 3/11 of our patients. A previously unreported feature is the occurrence of a conventional renal cell carcinoma component in one of our cases. Seven of our patients are currently well without signs of recurrence or metastasis, one had metastasis in a regional lymph node at the time of nephrectomy, one died of an unrelated condition, and two were lost to follow-up. CONCLUSIONS: We present 11 cases of spindle and cuboidal renal cell carcinoma, which is believed to be a distinctive morphological entity. Our cases were histologically, immunohistochemically and ultrastructurally similar to the previously reported cases of spindle and cuboidal renal cell carcinoma. In contrast to all previously reported cases of spindle and cuboidal renal cell carcinoma, we observed an association with nephrolithiasis in three of our cases; moreover, one of our tumours had a conventional renal cell carcinoma component and another revealed a metastatic focus in a regional lymph node. None of our patients died of the disease. This study confirms that spindle and cuboidal renal cell carcinoma has a low malignant potential.     

High incidence of papillary renal cell tumours in patients on chronic haemodialysis

Papillary and nonpapillary renal cell tumours can be differentiated according to their genetic constitution. In this study, their incidence in end stage kidney disease has been investigated histologically. Nonpapillary renal cell carcinoma was observed in 22 cases (51.2%) whereas papillary renal cell tumours were diagnosed in 21 (48.8%) of the 43 patients with end stage kidney disease. The incidence of papillary renal cell tumours in end stage kidney disease is significantly higher (χ²= 31.9; P <0.001) than in the general population (4.8%). Haemodialysis patients with nonpapillary and papillary renal cell tumours did not show significant differences in age, sex or size of tumour. However, patients with papillary renal cell tumours had received longer duration of haemodialysis than patients with nonpapillary renal cell carcinomas. These data suggest that not only different genetic events but also different aetiological factors are involved in the development of the two types of tumour in end stage kidney disease.     

Subclassification of renal cell neoplasms: an update for the practising pathologist

The classification of renal cell neoplasms has been extensively studied in the last decade, and a standardized nomenclature adopted. Although this system is based on a combination of genetic, histological and immunohistological features, in most cases accurate classification can be based on histological features alone. This review summarizes the key features of the tumours included in this system, and then focuses on diagnostic difficulties that can arise when using this system, as well as reviewing several recently characterized tumours that are not yet included.     

Pathological staging of renal cell carcinoma: a review of 300 consecutive cases with emphasis on retrograde venous invasion

Aims

Pathological staging of renal cell carcinoma (RCC) can be challenging compared to other cancer types, as invasion often manifests as finger‐like protrusions into vascular spaces or renal sinus tissue. Although prior studies have shown larger tumour size to be correlated highly with renal sinus invasion, prospective data on evaluating pathological stage are limited. We evaluated a large series reported by one urological pathologist.

Methods and results

Three hundred consecutive specimens were reviewed. Tumours larger than 5 cm were routinely sampled extensively or grossly re‐reviewed when no extrarenal extension was identified on initial examination. Apparent multifocal disease was assessed critically for intravascular spread. Retrograde venous invasion was reported in 15 of 300 (5%) cases, 13 of 15 of which were clear cell RCC. Of a total of 163 specimens with clear cell histology, only five of 34 (15%) tumours 7 cm or larger were reported as pT2, all of which had an explanatory comment indicating the absence of definitive extrarenal spread. In contrast, 15 of 20 (75%) pT2 tumours were non‐clear cell histology (papillary, chromophobe and translocation‐associated). Comparing pT3a or higher tumours, the median tumour size in cases with retrograde venous invasion was 8.0 cm, compared to 6.2 cm in cases without retrograde venous invasion (P = 0.005).

Conclusions

Our findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non‐clear cell histology (particularly papillary or chromophobe RCC).

     

Sarcomatoid collecting duct carcinoma of kidney diagnosed with urine and renal pelvic lavage cytology

A case of sarcomatoid collecting duct carcinoma (CDC) of kidney is presented, in which the diagnosis was made cytologically with voided urine and renal pelvis lavage. Cytology of hemorrhagic voided urine revealed highly atypical adenocarcinoma cells with reminiscent ductal structure, which suggested CDC as the most likely diagnosis. Computed tomography and magnetic resonance imaging demonstrated a left renal tumor, and selective lavage of left renal pelvis yielded spindle‐shaped, highly atypical cells that indicated sarcomatoid carcinoma. The diagnosis of renal cancer with urine cytology is challenging because of small number of tumor cells in the urine, which are often associated with degeneration. As the urinary cytologic findings of sarcomatoid CDC have not been reported, the characteristic cytologic findings of sarcomatoid CDC are described in detail, and the differential diagnoses with diagnostic pitfalls were discussed. Diagn. Cytopathol. 2010;38:603–606. 2009 Wiley‐Liss, Inc.     

A case of chromophobe renal cell carcinoma with sarcomatoid foci and a small daughter lesion

Chromophobe renal cell carcinoma (RCC), which has recently been recognized to be a distinct type of RCC, comprises approximately 5% of renal cell tumors. It has been hypothesized that the cells that comprise chromophobe RCC show a phenotype similar to that of intercalated cells of the collecting duct Although the number of research reports on this type of tumor has recently been increasing, only nine cases of chromophobe RCC showing sarcomatoid transformation have been described. Herein, a case of chromophobe RCC with sarcomatoid foci and a small daughter lesion is reported.     

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma

AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.     

Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT

We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.     

Papillary renal cell carcinoma with clear cell cytomorphology and chromosomal loss of 3p

AIMS: Cytogenetic studies on renal cell carcinomas (RCCs) have disclosed a correlation between chromosome aberrations and histomorphological features. Nevertheless, it is still controversial whether the cytomorphology of the tumour cells (clear cell, chromophilic, chromophobe) or their growth pattern (nonpapillary, papillary) is more discriminative for the combined histomorphological-cytogenetic classification of RCCs. METHODS AND RESULTS: Three RCCs with papillary growth pattern and clear cell cytomorphology were analysed by classical cytogenetics using standard G-banding techniques. Each tumour displayed clonal aberrations leading to loss of terminal 3p chromosomal segments. Monosomy 14 was also consistently found. Trisomy 17 was not observed in any of the tumours. CONCLUSIONS: This series of three RCCs consisting of clear cells with papillary architecture revealed chromosomal aberrations characteristic for the conventional (clear cell) RCC. Irrespective of the predominant papillary growth pattern, none of the cases were characterized by trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20 and loss of Y chromosome which are widely regarded as the most consistent genetic alterations for papillary RCC. Therefore, our cytogenetic findings provide evidence that papillary clear cell RCCs should be classified according to their cytomorphology rather than their growth pattern even when papillary architecture is prominent.     

CT多期增强扫描在肾细胞癌诊断中的应用

目的探讨CT多期增强扫描在肾细胞癌诊断中的应用价值。方法分析经手术病理证实的38例肾细胞癌患者,男27例,女11例,年龄25～72岁(平均48岁)。全部采用CT多期增强扫描。结果均为单肾单发病灶,形态上呈圆形或椭圆形35例,形态不规则3例;有明显假包膜26例(68%);密度呈较均匀稍低密度27例(71%);31例(82%)肿瘤呈重度强化,5例(13%)呈中度强化,2(5%)例呈轻度强化。35例(92%)强化不均匀。95%的病灶强化均呈"快进快出"型。CT分期准确率为95%。结论CT多期增强扫描是肾癌术前诊断与鉴别诊断的有效方法。