Renal cell carcinoma metastatic to the nasal cavity

Metastatic renal cell carcinoma of the nasal cavity is very rare. A 76-year-old man presented with epistaxis and admitted to our hospital. His past histories were right radical nephrectomy for renal cell carcinomas at the age of 68 years and brain infarction at the age of 75 years. Laryngoscopic examination revealed a red polyp of the right nasal cavity. Imaging modalities including CT and MRI also revealed a tumor measuring 2 x 3 x 2 cm. Angiography showed that the tumor is very hypervascular. Clinical diagnosis was angiogenic tumors including hemangioma, sinonasal hemangiopericytoma, and paraganglioma. A blood data showed anemia and low platerets, and bone marrow biopsy revealed myelodysplastic syndrome. A coiling embolization of the feeding artery was performed, and the tumor reduced markedly. The tumor was resected almost entirely. Pathologically, the tumor was 2 x 1.5 x 1.5 cm red tumor. The tumor cells had clear cytoplasm, and arranged in a trabecular pattern lined by a layer of endothelial cells. Atypia is mild. Immunohistochemically, the tumor cells were positive for pancytokeratin (AE1/3, CAM5.2), RCC ma, CD10, and Ki-67 (labeling=20%), but negative for CD34, factor-VIII-related antigen, CEA, EMA, melanosome (HMB45), S100 protein, p53, and HepPar-1. The pathological diagnosis was made without knowledge of kidney status. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. The patient is now free from tumor, and palliative chemoradiation is considered.     

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.     

Synchronous renal cell carcinoma and clear cell hepatocellular carcinoma mimicking metastatic disease

Double carcinomas of hepatocellular and renal cell carcinoma (RCC) are extremely rare, and among the reported cases, none of the hepatocellular carcinomas show clear cell change. We report a case of synchronous double primary clear cell tumor in the liver and the kidney of a 70-year-old male. The renal mass was a renal cell carcinoma of mixed clear and granular cell types, and the hepatic mass was a hepatocellular carcinoma with extensive clear cell change that mimicked a metastatic renal cell carcinoma. A simple battery of immunohistochemical stains composed of hepatocyte antigen, and CD10 was performed to make a definite diagnosis.     

Expression of CD9 and CD82 in clear cell renal cell carcinoma and its clinical significance

CD9 and CD82, members of the tetraspanin family, act as metastasis suppressors in many human malignant tumors, but the role of these molecules is not well known in clear cell renal cell carcinoma (CCRCC). This study was designed to evaluate the immunohistochemical expression of CD9 and CD82 in 644 cases of CCRCC and to determine the clinicopathologic and prognostic significance of their expression. The percentage of positive tumor cells was evaluated, and the expression was classified into 2 categories: low expression (less than 10% positive cells) or high expression (more than 10% positive cells) for CD9 expression and negative (no positive cells) or positive for CD82 expression. CD9 high expression was found in 303 (47.0%) patients, and CD82 positivity was found in 98 (15.2%) patients. High expression of CD9 was statistically associated with older patients (p = 0.003). The cases showing positive immunoreactivity for CD82 exhibited a high stage (p < 0.001) and high nuclear grade (p < 0.001). The overall, cancer-specific and progression-free survival rates were significantly higher in patients with a CD82-negative profile compared to patients with a CD82-positive profile (p < 0.001). Although the biological function of CD82 in CCRCC remains unclear, the CCRCC patients with CD82 positive expression show poor prognosis.     

Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer

This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p < 0.05) in squamous cell carcinoma. In adenocarcinomas, HAb18G/CD147 expression was associated with male gender, tumor diameter, differentiation, lymph node status, distant metastasis status, and clinical stage (p < 0.05). HAb18G/CD147 expression with higher PU was predominantly localized in the tumor cell membranes rather than in cytoplasms. In squamous cell carcinomas, membranous localization of HAb18G/CD147 was linked to distant metastasis status and TNM stage (p < 0.05). Cytoplasmic localization of HAb18G/CD147 was associated with male gender and smoking history. In adenocarcinomas, membranous localization of HAb18G/CD147 correlated with tumor diameter, differentiation and distant metastasis (p < 0.05). Univariate analysis indicated that patients with high HAb18G/CD147 expression and membranous localization predicted poor prognosis in both squamous cell carcinomas and adenocarcinomas. Multivariate analysis showed that lymph node status (HR = 1.762, 95%CI 1.105–2.811, p = 0.017), distant metastasis status (HR = 3.789, 95%CI 2.196–6.539, p = 0.000), expression (HR = 6.632, 95%CI 2.457–17.904, p = 0.000), and localization (HR = 0.520, 95%CI 0.341–0.794, p = 0.002) were good or excellent independent predictors of patient survival. HAb18G/CD147 is a biomarker characterizing progression and survival of NSCLC. More importantly, its cellular localizations should be considered in the analysis of clinicopathological characteristics and prognostic factors in NSCLC.     

Renal tumors with clear cells. A review

The spectrum of primary renal tumors in which clear cells may appear is revisited in this review. The pathologist's viewpoint of this topic is pertinent because not all the tumors with clear cells are carcinomas and not all renal cell carcinomas with clear cells are clear cell renal cell carcinomas. In fact, some of them are distinct entities according to the new WHO classification. The morphological approach is combined with genetics. Renal cell carcinoma related to von Hippel–Lindau disease is reviewed first because many of the genetic disorders underlying this disease are also present in sporadic, conventional renal cell clear cell carcinomas. Subsequently, conventional renal cell clear cell carcinomas, familial, non von Hippel–Lindau-associated renal cell carcinomas, translocation carcinomas, hereditary papillary renal cell carcinomas, carcinomas associated to tuberous sclerosis and to Birt–Hogg–Dubé syndrome, chromophobe renal cell carcinomas, carcinomas associated with end-stage renal disease, and clear cell tubulopapillary carcinomas are reviewed. Finally, epithelioid angiomyolipoma is also considered in this review.     

Low-grade renal cell carcinoma arising from the lower nephron: a case report with immunohistochemical, histochemical and ultrastructural studies

Most renal cell carcinomas (RCC) are composed of clear cells with sinusoid-like vasculatures and originate from the proximal tubule. On the other hand, collecting duct carcinoma (CDC) and chromophobe RCC are thought to originate from the lower nephron. In the present study, we present a case of unusual RCC. The patient was a 68-year-old Japanese woman who had developed general fatigue with hematuria. Computed tomography revealed a left renal tumor suggesting sarcoma. The resected tumor was located in the renal parenchyma, measuring 12 x 10 x 8 cm in size. Histologically, the tumor consisted principally of cuboidal cells forming parallel or radiating arrays, continuous with the spindle-shaped cells. Most parts of the tumor showed hemorrhagic necrosis. Immunohistochemically, tumor cells were positive for high molecular weight cytokeratins, vinculin, vimentin, CD15 and epithelial membrane antigen, and showed affinities with some kinds of lectins. N- and E-cadherins and beta-catenin were diffusely positive in tumor cells. Nuclear positivity for Ki-67 and p53 protein were approximately 2.0 and 1.7%, respectively. Considering its morphological and histochemical natures, this tumor is considered to have originated from the lower nephron, which is unique for a tumor of low-grade malignancy.     

Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma

Osteopontin (OPN) is a phosphoglycoprotein implicated in tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumor cells. The aim of this study was to analyze the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumor cells.Expression of OPN protein and p65 NF-κB subunit was analyzed immunohistochemically in 87 CCRCC samples, and compared mutually and with apoptotic index. Expression of OPN mRNA was analyzed using quantitative real-time PCR and compared with OPN and NF-κB protein expression in 22 CCRCC samples.Statistical analysis showed an association of p65 NF-κB with OPN mRNA (p = 0.015) and protein (p < 0.001). Also, we found an inverse relationship of OPN with NF-κB protein expression and apoptotic activity of tumor cells (p = 0.006 and p = 0.022, respectively). Our results indicate that p65 NF-κB signaling pathway may be involved in OPN-mediated CCRCC progression, partly by protecting tumor cells from apoptosis. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC.     

Expression of prostate-specific membrane antigen in renal cortical tumors.

Prostate-specific membrane antigen is a type II membrane glycoprotein that is expressed in benign and neoplastic prostatic tissue and has been recently shown to be also expressed in the neovasculature of various solid malignant tumors including renal cell carcinoma. Renal cell carcinoma is a heterogeneous group of tumors with distinct morphologic and genetic characteristics and clinical behaviors. We performed immunohistochemical studies on formalin-fixed, paraffin-embedded archival material from 75 nephrectomies, using antibodies 13D6 against prostate-specific membrane antigen and CD31 against endothelial cells. The study included 30 clear cell renal cell carcinomas, and 15 of each of papillary and chromophobe renal cell carcinoma and oncocytoma. The extent and intensity of staining were assessed semiquantitatively. In all cases, immunoreactivity was detected only in the tumor-associated neovasculature and not in tumor cells. Clear cell renal cell carcinoma showed the most diffuse staining pattern, where 24/30 cases or 80% had >50% reactive vessels, followed by chromophobe renal cell carcinoma (9/15; 60%) and oncocytoma (5/15, 33%). No diffuse staining was detected in any of the papillary renal cell carcinomas and only focal staining was detected in 11 cases (11/15; 73%). Staining intensity was the strongest in clear cell renal cell carcinoma (25/30; 83%) followed by chromophobe renal cell carcinoma (9/15; 60%), oncocytoma (8/15, 53%) and papillary renal cell carcinoma (5/15; 33%). In summary, prostate-specific membrane antigen is expressed in tumor-associated neovasculature of the majority of renal cortical tumors and is most diffusely and intensely expressed in clear cell renal cell carcinoma and least in papillary renal cell carcinoma. The differences in the expression of prostate-specific membrane antigen in renal cell carcinoma subtypes provide further evidence of the biological diversity of these tumors, and diagnostic and therapeutic applications of such expression can be expanded to include subtypes of renal cell carcinoma.     

Renal tumor with alpha b crystallin expression

In human, proximal convoluted tubules and thin limbs of Henle show expression of αB crystallin. Renal cell carcinoma also showed expression of αB crystallin in previous reports. We aimed to study the association between αB crystallin expression and renal cell carcinoma and urothelial carcinoma. Furthermore, we also investigated αB crystallin expression depending on the subtype of renal cell carcinoma and examined the relationship between αB crystallin expression and survival in patients with renal cell carcinoma. In our study, αB crystallin expression was different according to the type of tumor. A greater proportion of the clear cell type (52/77, 67.5%) and papillary type (4/4, 100%) showed reactivity compared to the chromophobe type (0/10, 0%). In the present study, a significantly greater number of renal cell carcinomas showed strong expression of αB crystallin (56/91, 61.5%) compared to urothelial carcinoma (P=7.967e-07). Therefore, αB crystallin might be a significant marker of renal cell carcinoma and might help to determine the type of renal tumor in cases of poorly differentiated kidney lesions and metastatic lesions. αB crystallin expression was not related to overall survival in univariate and multivariate models. In our study, alpha B crystallin could not be considered a prognostic marker of renal cell carcinoma.     

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.     

Renal Cell Carcinoma Metastatic to the Thyroid Gland: A Comparative Molecular Study Between the Primary and the Metastatic Tumor

A case of renal cell carcinoma metastatic to the thyroid gland is presented. The thyroid tumor showed typical features: clear cells arranged in nets with a prominent sinusoidal vascular pattern. The histologic appearance was identical to the renal tumor removed 6 yr before. A comparative molecular study between the primary and the metastatic tumor showed a common profile with a loss of heterozygosity at identical loci on chromosome 3, which provided further support to the metastatic nature of the thyroid tumor. However, the frequent existence of allele losses on chromosome 3p in both renal cell carcinomas and primary thyroid follicular carcinomas rest some force from such a molecular approach to the differential diagnosis of thyroid tumors that contain a predominant population of clear cells.     

CD34 immunostaining enhances a distinct pattern of intratumor angiogenesis with prognostic implications in clear cell renal cell carcinoma

Clear cell renal cell carcinoma is an aggressive neoplasm related to VHL gene inactivation. The molecular events derived from this initial alteration lead to a permanent intracellular pseudo‐hypoxic status that stimulates vascular proliferation. The resulting increased intratumor angiogenesis is the target of most modern therapies. Although intratumor angiogenesis has received full attention in the last years, few studies have focused on its potential importance from a strict morphological approach. Intratumor angiogenesis has been analyzed in a retrospective series of clear cell renal cell carcinomas (n = 208) with long‐term follow‐up (n = 177). Two different patterns of angiogenesis have been highlighted with CD34 at the front of tumor invasion, termed continuous and discontinuous, respectively. The continuous pattern of angiogenesis showed a complete microvascular network surrounding totally tumor nests. Conversely, the discontinuous pattern displayed an incomplete network around tumor nests. The continuous pattern was associated to shorter 5‐year (p = 0.00064, hazard ratio = 2.8) and 15‐year (p = 0.014, hazard ratio = 1.7) survivals. Cox regression multivariate analysis also showed that the continuous pattern (p = 0.016373) remains a significant variable when considered together with grade (p = 0.001755) and stage (p = 0.000952). These findings support the notion that a continuous CD34⁺ pattern of intratumor angiogenesis may be useful for pathologists in predicting tumor behavior in clear cell renal cell carcinomas.     

Fine-needle aspiration of chromophobe renal-cell carcinoma metastatic to the thyroid gland

Chromophobe renal cell carcinoma is an unusual variant of renal carcinoma that has less aggressive behavior than clear cell carcinomas. There are few documented cases of metastases, none of which occurred in the thyroid gland. A case is presented of chromophobe renal cell carcinoma metastatic to the thyroid eight years after right nephrectomy, suspected by FNA-biopsy and confirmed histologically. Although metastases of chromophobe renal cell carcinoma are rare, they may also present in thyroid, even many years after primary tumor diagnosis, just like clear cell carcinomas. Even though the FNA cytology of chromophobe renal cell carcinoma has distinctive features, in the context of the thyroid, it can be mistaken for a primary tumor of that organ. In our case, the history of a previous renal tumor was essential in suggesting a metastatic lesion, and histologic and ultrastructural features allowed its precise identification.     

Large cell neuroendocrine carcinoma with sarcomatous changes of the endometrium: A case report with immunohistochemical studies and molecular genetic study of KIT and PDGFRA

The author herein reports a very rare case of large cell neuroendocrine carcinoma (LCNEC) with sarcomatous changes of the endometrium. A 40-year-old woman was admitted to our hospital because of abnormal uterine bleeding. Gynecologic examination and imaging modalities revealed a polypoid tumor of the uterine corpus. Uterine curettage biopsy revealed a sarcomatous undifferentiated carcinoma. Simple hysterectomy, salpingo-oophorectomy, extensive lymph node dissection, and omentectomy were performed. The patient was diagnosed as having FIGO stage Ib (T1N0M0) carcinoma, and adjuvant chemotherapy was performed. The patient is now alive 16 months after the operation. Pathologically, a polypoid tumor measuring 3×2×2 cm³ was found in the uterine corpus. Histologically, the tumor consisted of relatively large-sized carcinoma cells without differentiation. The tumor cells have abundant cytoplasm and prominent nucleoli. It was composed of a spindle cell component (40%) and an epithelioid component (60%). A gradual transition between the two was recognized. Immunohistochemically, both elements showed the same immunophenotypes. The carcinoma cells were positive for cytokeratin, vimentin, CA125, CD34, estrogen receptor, progesterone receptor, p53 protein, Ki-67 antigen (80%), synaptophysin, CD56, KIT, and PDGFRA. They were negative for epithelial membrane antigen, CEA, desmin, S100 protein, melanosome, α-smooth muscle actin, chromogranin, and neuron-specific enolase. A molecular genetic analysis revealed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The final diagnosis was LCNEC with sarcomatous changes.     

Analysis of local immunity in squamous cell carcinoma of the tongue and lower lip

Antitumor immunity plays an important role in the development of and protection against malignancy. In general, patients with cancer are known to be immunologically compromised. The objective of this study was to evaluate local immunity in squamous cell carcinomas (SCCs) of the tongue and lower lip by immunohistochemistry, using anti-CD3, -CD4, -CD8, -CD25 and -ζ antibodies. Immunoexpression at the invasive front was compared considering anatomical tumor location and metastasis. The CD4/CD8 ratio was calculated for each case and associated with the variables. CD3+, CD4+, CD8+ and CD25+ cell counts were higher in SCCs of the lower lip and anti-ζ immunostaining was more evident in non-metastatic cases. CD8+ and CD25+ cell counts were also significantly correlated with tumor location (p = 0.004 and p = 0.004, respectively), with the observation of a larger number of these cells in SCCs of the lower lip. The CD4/CD8 ratio showed no significant association with metastasis or anatomical location. In conclusion, the clinical behavior of the oral SCC cases studied might be partially related to the immunohistochemical profile of the inflammatory infiltrate present at the invasive front.     

Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade

Carbonic anhydrase IX (CAIX), a hypoxia-induced protein, is expressed in some renal tumors. We evaluated its immunohistochemical expression in 317 primary and 42 metastatic renal neoplasms (186 clear cell, 52 papillary, 35 chromophobe, 47 unclassified, and 15 Xp11.2 translocation renal cell carcinomas [RCCs]; 26 oncocytomas; 2 metanephric adenomas; 1 urothelial carcinoma; 1 mixed epithelial and stromal tumor; and 1 angiomyolipoma); 7 neoplasms were unknown as to whether they were primary or metastatic. We also correlated expression with tumor type and grade. Variable staining was seen in clear cell, papillary, unclassified, and Xp11.2 translocation carcinomas. One chromophobe carcinoma had focal expression. No staining was seen with other tumors. An association was found between high expression and clear cell vs non-clear cell carcinomas with all cases (P < .01) and primary (P < .01) cases. An association between CAIX expression and grade (P < .01) in primary clear cell carcinomas was found. CAIX expression is more common in clear cell RCC than other renal tumor types and is associated with grade.     

Expression of EphA2 protein is positively associated with age,tumor size and Fuhrman nuclear grade in clear cell renal cell carcinomas

The receptor tyrosine kinase of EphA2 has been shown frequently overexpressed in various types of human carcinomas, which implicated that it plays important roles in carcinogenesis. Although EphA2 protein expression has been investigated in many types of human carcinomas, the relationship between the expression of EphA2 protein in clear cell renal cell carcinoma was not well documented. In the present study, using specific anit-EphA2 polyclonal antibody and immunohistochemistry, we evaluated EphA2 protein expression levels in clear cell RCC specimens surgically resected from 90 patients. Our results shows that EphA2 protein was positively expressed in all normal renal tubes of 90 samples (100%, 3+), which was expressed at low levels in renal cortex but high levels in the collecting ducts of the renal medulla and papilla. EphA2 was negatively or weakly expressed in 30 out of 90 samples (33.3%, 0/1+), moderately expressed in 24 samples (26.7%, 2+) and strongly expressed in 36 samples (40%, 3+). Expression of EphA2 was positively associated with age (P=0.029), tumor diameters (P<0.001) and Fuhrman nuclear grade (P<0.001). Our results indicate that EphA2 variably expressed in clear cell renal cell carcinomas. High expression of EphA2 was more often found in big size and high nuclear grade tumors, which indicated EphA2 protein may be used as a new marker for the prognosis of clear cell renal cell carcinoma.