Sarcomatoid renal cell carcinoma in a young adult

Sarcomatoid renal cell carcinoma (SRCC) is an uncommon, aggressive renal cell carcinoma (RCC) accounting for 1.2% to 12.3% of renal cell carcinomas. SRCC may arise from any RCC subtype as it probably results from the de-differentiation of any renal epithelial malignancy. SRCC is characterised by a rapid progression and high metastatic rate. Currently there is no specific effective treatment for it. We report a new case of a 32-year-old man presented with two months backache. Ultrasound revealed a 7.5 cm heterogeneous mass at the inferior pole of the left kidney. A nephrectomy was performed. Histological study diagnosed a sarcomatoid renal cell carcinoma. The patient was doing well 6 months after initial surgery and then was lost to follow-up.     

Adult renal cell carcinoma with rhabdoid morphology represents a neoplastic dedifferentiation analogous to sarcomatoid carcinoma

Renal cell carcinoma (RCC) with rhabdoid morphology (RCC-RM) is a recently described variant of RCC, which has an aggressive biologic behavior and poor prognosis, akin to sarcomatoid RCC. The current World Health Organization classification of RCC does not include the rhabdoid phenotype as a distinct histologic entity. The aim of this study is to investigate whether RCC-RM represents a dedifferentiation of a classifiable-type World Health Organization RCC or a carcinosarcoma with muscle differentiation. We reviewed 168 cases of RCC obtained between 2003 and 2008. From these cases, 10 (6%) were found to have areas of classic rhabdoid morphology. Immunohistochemistry for cytokeratin, epithelial membrane antigen, desmin, CD10, and CD117 was performed in each case using the labeled streptavidin-biotin method. Rhabdoid differentiation was identified in association with conventional-type RCC (9) and with unclassifiable-type RCC with spindle cell morphology (1). In all cases, both the rhabdoid and nonrhabdoid tumoral areas were positive for cytokeratin and epithelial membrane antigen and negative for desmin. Cytokeratin positivity in the rhabdoid areas was focal. In cases associated with conventional-type RCC, CD10 was positive in both the rhabdoid and nonrhabdoid foci. CD117 was negative in these tumors. The unclassifiable-type RCC with spindle cell morphology was negative for both CD10 and CD117. The similar immunophenotype between the rhabdoid and nonrhabdoid tumoral foci supports the origin of the rhabdoid cells from the classifiable-type RCC. Areas of rhabdoid morphology do not represent muscle metaplastic differentiation. Renal cell carcinoma with rhabdoid morphology may represent a dedifferentiation of a classifiable-type RCC, similar to that of sarcomatoid differentiation. The recognition of RCC-RM is important as it allows for the inclusion of these high-grade malignancies into a category associated with poor prognosis despite lacking the spindle cell component classically identified as sarcomatoid change.     

Feasibility of differential diagnosis of kidney tumors by comparative genomic hybridization of fine needle aspiration biopsies

The association of a genetic analysis that could improve the diagnostic accuracy of renal cell tumors in biopsy samples would allow better‐informed therapeutic decisions. We performed comparative genomic hybridization (CGH) on an ex vivo fine‐needle aspiration (FNA) biopsy and a tumor fragment obtained from 75 patients consecutively diagnosed with renal tumors and subjected to radical nephrectomy. The pattern of genomic changes by CGH was used blindly to classify the renal tumors and the genetic findings were subsequently compared with the histopathologic diagnosis. In particular cases, including in two carcinomas with morphologically distinct tumor areas, we performed FISH with several locus‐specific probes, and looked for VHL point mutations, exonic rearrangements, or promoter methylation. CGH was successful in 82.7% FNA biopsies and in 96% tumor fragments, with the former allowing genetic diagnosis in 75% of renal cell tumors. The genetic and the initial histological classification differed in two renal neoplasias, but the genetic diagnosis was confirmed after review. The genetic pattern correctly diagnosed 93.5% of clear cell renal cell carcinomas (RCC), 61.5% of chromophobe RCC, 100% of papillary RCC, and 14.3% of oncocytomas, with the negative predictive value being 93.9, 90.7, 100, and 90.2%, respectively. The positive predictive value and specificity of copy number profiles was 100%. We demonstrate that genetic diagnosis by CGH on FNA biopsies can improve differential diagnosis in patients with kidney tumors. © 2010 Wiley‐Liss, Inc.     

Comparison of PAX-2, RCC antigen, and antiphosphorylated H2AX antibody (gamma-H2AX) in diagnosing metastatic renal cell carcinoma by fine-needle aspiration

Diagnosing metastatic renal cell carcinoma (RCC) by fine-needle aspiration (FNA) can be challenging. Existing antibodies supporting a diagnosis of RCC, including CD10 and RCC-Ma, have problems with specificity and interpretation. In this report, we evaluate the use of two newer immunostains, PAX-2 and gamma-H2AX, which to our knowledge have not been studied in FNA material, in the diagnosis of metastatic RCC and in comparison with RCC-Ma. 29 cases of metastatic RCC were identified as well as a TMA of an additional 30 RCC cases. In the case cohort, RCC-Ma in a membranous pattern of staining identified 15/27 (56%) metastatic RCC, although interpretation was made difficult in many cases due to focality of staining and non-specific cytoplasmic staining. PAX-2 stained 23/29 (79%) of tumors in a nuclear stain, most strongly. Gamma-H2AX stained 19/26 (73%) of metastatic RCC strongly in a nuclear stain. In the TMA, strong, diffuse nuclear staining with gamma-H2AX was present in 22/30 RCC (73%). If weak staining was also included as positive, 26/30 (87%) were positive. PAX-2 stained RCC TMA with a lower percentage at 56%, including weaker staining intensity. Both PAX-2 and gamma-H2AX demonstrated patchy staining of normal renal tubules, PAX-2 to a greater extent. Both PAX-2 and gamma-H2AX are sensitive markers for the diagnosis of metastatic RCC, with improved ease of interpretation when compared with RCC-Ma. A combination of all 3 markers identified 87% of cases, and failure to stain for both PAX-2 and gamma-H2AX suggests against, but does not disprove, a diagnosis of RCC.     

Expression of CA15–3 in renal cell carcinoma

CA15–3 expression was analyzed in renal cell carcinoma (RCC) from the standpoint of the histogenesis of RCC. Tissue sections from surgical specimens of 12 cases of clear cell type RCC and from autopsy specimens of eight fetal kidneys were stained by an indirect immunoperoxi-dase method using DF-3. All the RCC cases stained positively for CA15–3, with 10 of the 12 cases showing strong, diffuse immunoreactivity on the cell membrane. Expression of CA15–3, as well as other markers such as epithelial membrane antigen, neuron-specific enolase, glandular cytokeratin and other lectins, suggest a more complicated histogenesis of RCC, rather than a simple proximal tubular origin.     

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.     

The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study

Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewis(y)), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4, 8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.     

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.     

Mucinous tubular and spindle-cell carcinoma of the kidney

4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of the kidney were studied. The patients' age was 43 to 87 years. Microscopically, this tumor comprised two major cell populations. One of them involved spindle cells with a sparse cytoplasm, which were arranged in the fascicular pattern, often resembling low-grade smooth muscle tumors. The other population was small cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic activity was low. Only one tumor had both cell components. The other three tumors were represented by the second type cells. Immunohistochemical staining with avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA, and CD10. All cases were stained positively with antibodies to the cytokeratins AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney should be differentiated from angiomyolipoma with the preponderance of a leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma, and renal cell carcinoma with sarcomatoid differentiation.     

Sarcomatoid renal cell carcinoma of papillary origin. A case report and cytogenic evaluation

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non-clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non-clear cell origin.     

Sarcomatoid carcinoma of the urinary bladder. A clinicopathologic analysis of 12 cases and review of the literature

Twelve carcinomas of the urinary bladder with a prominent component of spindle-shaped cells (sarcomatoid carcinomas) that arose in patients from 60 to 83 (average, 71.5 years) years of age are reported. The seven male and five female patients typically complained of hematuria. Seven tumors were sessile and five were polypoid. On microscopic examination, the malignant spindle cells merged with in situ transitional cell carcinoma or various forms of invasive carcinoma, including transitional cell carcinoma (11 cases), adenocarcinoma (2 cases), squamous cell carcinoma (2 cases), and small cell undifferentiated carcinoma (2 cases). Immunocytochemical stains were performed in 11 cases; the spindle cells stained for cytokeratin, epithelial membrane antigen, and vimentin. Limited follow-up in this series does not allow for conclusions concerning differences in behavior between sarcomatoid carcinoma and conventional transitional cell carcinoma of similar grade and stage. However, the typically deep invasion of the former tumors and their histologic features indicate that they are highly aggressive neoplasms.     

Expression of renal cell carcinoma antigen (RCC) in renal epithelial and nonrenal tumors: diagnostic Implications.

Antibody to renal cell carcinoma (RCC) antigen, a normal human proximal brush border antigen, has recently become commercially available and reported to be highly specific and a relatively sensitive marker for RCC. Of the nonrenal tumors occasional carcinomas have been reported to express RCC, notably breast carcinoma. Using tissue microarrays, we investigated the use of RCC on a large number of renal epithelial neoplasms (RENs) and nonrenal tumors, especially those potentially confused with REN. Three tissue microarrays containing 241 REN samples, 192 samples of a wide variety of neoplasms and 170 adrenal tumor samples, respectively, were stained with RCC monoclonal antibody. RCC expression was scored for staining intensity and percentage expression. Out of 241 REN, 173 were positive for RCC (sensitivity 72%): clear cell 72%, papillary 95%, chromophobe 91%, unclassified 85%, oncocytoma 75%, sarcomatoid 20%, and metastatic RCC 40%. The overall immunostaining intensity was consistently much higher in papillary and clear cell RCC than in other tumors. Seventy-six out of 362 nonrenal tumor samples demonstrated either focal or diffuse expression for RCC (specificity 79%). These included: adrenocortical neoplasms 37/170 (22%), colonic 11/29 (37.5%), breast 9/27 (33%), prostate 5/18 (27.7%), ovary 2/17 (11.7%), melanoma 3/18 (16.6%), lung 3/21 (14.2%), and parathyroid 3/3 (100%). RCC expression was seen equally among adrenal adenoma and carcinoma group. Eight out of 28 (28.5%) normal adrenal cores also stained for RCC. RCC is a relatively useful marker in the differential diagnosis of REN only if used in a panel with other positive and negative markers. RCC does not reliably differentiate REN, especially classic clear cell type, from adrenocortical neoplasms, which are frequently confused due to close anatomic proximity and similar morphology. RCC also does not reliably differentiate subtypes of renal epithelial neoplasms.     

Chromophobe renal cell carcinoma with sarcomatoid change. A case report

Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.     

Typing of renal tumors by morphological and immunocytochemical evaluation of fine needle aspirates

Image-guided fine needle aspiration biopsy (FNAB) of renal masses can accurately evaluate malignancy. Adjunct methods are needed for accurate typing of renal cell carcinomas (RCC) and benign neoplasms. Cytopathological diagnoses of 79 routine ultrasound-guided FNAB of renal lesions were compared to consequent histological diagnosis and size of tumors. Cytology samples were sufficient for immunocytochemical subtyping in 43 cases (54.4%). The median tumor size was 2.8 cm, with 57 cases (76%) smaller than or equal to 4 cm. When a panel of immunocytochemical stainings (vimentin, CK7, CD117, P504S) was applied, accurate diagnoses were obtained in 11/12 (91.7%) of clear cell RCC (CRCC), 14/17 (82.3%) of papillary RCC (PRCC) and 5/7 (71.4%) of chromophobe RCC (ChRCC), respectively. Substantial cell pleomorphism with unusual immunostainings led to erroneous diagnosis of pheochromocytoma in CRCC with eosinophilic cytoplasm. Only 30% of CRCC were correctly diagnosed in the group without immunostaining, seven were suspicious for CRCC, and the remainder had unrepresentative material for CRCC. Cytopathological diagnoses were less accurate in oncocytomas (n = 11), regardless of immunocytochemical staining. Cystic nephromas (n = 2) and MEST (n = 1) were overdiagnosed as suspicious and positive for PRCC, respectively, with immunocytochemical staining not assisting in correct diagnosis. RCC can be accurately typed as CRCC, PRCC or ChRCC in fine needle aspirates in a routine clinical setting if the cellular material is sufficient and a panel of antibodies is used (vimentin, CK7, P504S, CD117). The classification of oncocytomas and cystic nephromas is not reliable since atypical morphology and immunocytochemical reactions overlap with RCC.     

MET expression in sporadic renal cell carcinomas

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.     

肾肉瘤样癌研究进展

肾肉瘤样癌(sarcomatoid renal cell carcinoma,sRCC)是肾细胞癌(renal cell carcinoma,RCC)亚型的一种变异,不是一个单独的类型,它可以发生在任何肾细胞癌亚型。临床上讲,肾肉瘤样癌具有生长迅速、诊断时高转移率、对治疗反应差、预后差和较短总生存期的特点。由于对肾肉瘤样癌研究有限,导致在理解和治疗这种肿瘤方面进步微小。因为这个疾病占晚期疾病的10%~20%,占肾细胞癌死亡率的首位,所以肾肉瘤样癌是一个需要所有临床医生熟悉的重要疾病。     

Renal cell carcinomas with intratumoral fat and concomitant angiomyolipoma: potential pitfalls in staging and diagnosis

Intratumoral fat and angiomyolipomas (AMLs) occurring within renal cell carcinomas (RCCs) have rarely been reported but may be mistaken for tumor invasion into perinephric or renal sinus fat or misdiagnosed as tumor exhibiting sarcomatoid differentiation. We report 16 such cases. In 14 RCC cases, there was intratumoral fat, 9 of which had fat located peripherally near the capsule (n = 6), renal sinus (n = 1), or both (n = 2). Inflammatory infiltrates and osseous metaplasia were identified in the intratumoral fat in 7 and 8 cases, respectively. Two cases had intratumoral AML foci located at the periphery of RCC. Intratumoral fat or AML at the periphery of RCC simulated the invasion into the fat, while the smooth muscle component of AML resembled spindle cell, or sarcomatoid, differentiation. Our study highlights the potential pitfalls in staging and diagnosis when intratumoral fat or AML is found within RCC.     

An autopsy case of hepatic sarcomatoid tumor: Immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-α₁-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immuno-histochemistry; many tumor cells were strongly immuno-reactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and u,-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.     

Co-expression of cytokeratin and vimentin intermediate-sized filaments in renal cell carcinomas

Summary The expression of intermediate-sized filaments (IF) was examined by immunocytochemical methods in 40 primary renal cell carcinomas and compared with the IF distribution in the normal adult human kidney. All tumours stained positively with cytokeratin IF antibodies. Co-expression of cytokeratins and vimentin was observed in 21/40 (52,5%) renal carcinomas. Double immunofluorescence labelling demonstrated that in most of these cases tumour cells contained both cytokeratin and vimentin type IF. In normal human kidneys, cells of the various tubular segments disclosed a positive reaction with cytokeratin antibodies in a different intensity and intracellular localization. Co-expression of cytokeratin and vimentin IF in normal adult human kidneys has never been observed. From a histogenetic point of view, co-expression of cytokeratins and vimentin in renal cell carcinoma obviously represents an atavistic phenomenon since vimentin is re-expressed by these tumour cells during neoplastic transformation. This finding indicates the metanephric origin of the renal parenchyma. In surgical pathology the possibility of very rare co-expression of cytokeratin and vimentin IF within tumour cells should be considered, particularly in the differential diagnosis of clear cell carcinomas.Dedicated to Prof. Dr. K. Goerttler on the occasion of his 60th birthday