Renal Nodes Research Articles

Chromophobe renal cell carcinoma with prominent lymph node metastasis and polysomy of chromosome 21: poorly differentiated form or “presarcomatoid” form?

Lymph node metastasis of chromophobe renal cell carcinoma (RCC) is extremely rare. It has been recently reported that sarcomatoid chromophobe RCC frequently show polysomy of chromosomes 1, 2, 6, 10, and 17. In this article, we report an unusual case of chromophobe RCC. A 42-year-old Japanese woman presented with hematuria and complained of inguinal pain 2 months after the initial symptoms. Radical nephrectomy and renal hilar lymphadenectomy were performed. The tumor was 8 cm in greatest diameter; its cut surface was beige in color. Large metastasis to the renal hilar lymph node was identified. Histological examination of the right renal tumor met the criteria of chromophobe RCC. In addition to histological findings of typical chromophobe RCC, small cell foci, comedo-like necrosis, trabecular growth pattern, and sclerosing stroma were observed. However, no sarcomatoid foci were identified anywhere, despite extensive tumor sampling including lymph node lesions. Immunohistochemically, neoplastic cells were positive for E-cadherin and CD117 (c-kit). Ultrastructurally, tumorous cells contained abundant mitochondria and cytoplasmic microvesicles. Fluorescence in situ hybridization showed monosomy of chromosomes 2 and 10 and polysomy of chromosome 21. Finally, we suggest that this tumor may show the poorly differentiated or presarcomatoid form of chromophobe RCC.

Integrated Lymphography using Fluorescence Imaging and Magnetic Resonance Imaging in Intact Mice

We assessed lymph drainage in living mice by an integrated imaging method using fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Mice were subcutaneously injected with quantum dots and gadofluorine 8 into the right rear footpad. They were fixed on a transparent flat plate and underwent FLI and MRI successively. Small markers were attached to the mouse surface for spatial coregistration, and image fusion of FLIs and MRIs was performed. Two-dimensional fluorescence reflectance imaging was used for FLI. FLI and MRI provided generally consistent results and demonstrated lymphatic flow to the popliteal, sacral, and iliac lymph nodes in most mice and to the renal, inguinal, and lumbar-aortic lymph nodes in some mice. On the fusion images, the locations of the lymph nodes in the mouse trunk were in good agreement between FLI and MRI, indicating successful spatial registration even for the deep structures. The popliteal node tended to be visualized a little farther caudally in FLI than in MRI, presumably because the overlying tissues were thicker in the cranial portion. Integrated FLI/MRI lymphography with image fusion appears to be a useful tool for analysis of the murine lymphatic system.

Clinical Pictures and Novel Mutations of WT1-Associated Denys–Drash Syndrome in Two Chinese Children

Denys–Drash syndrome (DDS) is characterized by early onset of nephropathy, genitalia malformation, and Wilms’ tumor, where WT1 is the gene that is mutated in most patients. We report two de novo mutations in WT1 found in two Chinese DDS children. Patient 1 was a boy with complete DDS who was presented with progressive nephropathy, unilateral Wilms’ tumor, bilateral cryptorchidism, and renal histology showing diffuse mesangial sclerosis (DMS). When the patient was 24 months old, a liver ultrasound showed multiple nodules, and the patient died of pneumonia 1 month later. The de novo novel mutation, c.1130A>T (p.His377Leu), was identified; the mutation replaces histidine with leucine in the zinc finger (Znf) structure and is predicted to change the local spatial structure of the protein. Patient 2 had 46 XX with incomplete DDS and presented with normal genitalia, proteinuria, unilateral Wilms’ tumor with renal pedicle lymph node metastasis, and renal histology showing DMS. Her renal function remains normal after 48 months. A de novo mutation, c.1168C>T (p.Arg390Term), was identified; it truncates 60 amino acids at the C terminus, and it is predicted to result in loss of the DNA-binding capacities of the WT1 protein.

Can a Durable Disease-Free Survival be Achieved With Surgical Resection in Patients With Pathological Node Positive Renal Cell Carcinoma?

Patients with isolated regional nodal metastases from renal cell carcinoma are a distinct cohort for which resection of involved lymph nodes may be therapeutic. We assessed the outcomes of patients treated at our institution with pathological node positive renal cell carcinoma without concomitant metastatic disease (T(any)N+M0). A total of 2,521 patients with nonmetastatic renal cell carcinoma (T(any)N(any)M0) of any histological subtype treated with nephrectomy were identified between 1995 and 2009. Pathological regional node positive disease in the absence of clinically detectable metastases (T(any)N(1-2)M0) was present in 68 patients (2.7%) and these patients formed our study cohort. Patients were assessed for timing and location of recurrence, disease specific survival and overall survival. Multivariate Cox regression analysis was performed to define factors predictive of recurrence and overall survival. Of the 68 patients with T(any)N(1-2)M0 renal cell carcinoma 22.1% were free of disease at a median followup of 43.5 months. In those patients experiencing recurrence, disease was detected within the first 4 months after surgery in 51% and was most commonly detected at multiple organ sites. The Kaplan-Meier estimated 5-year overall survival and disease specific survival was 37% and 39%, respectively. Predictors of a favorable outcome included an Eastern Cooperative Oncology Group performance status of 0, single node involvement, absence of sarcomatoid features and papillary histology. Nephrectomy with lymph node dissection can provide a durable disease-free survival in a proportion of patients with regionally advanced renal cell carcinoma and limited lymph node metastases.

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

IntroductionMRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging.MethodsPhase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences.ResultsSNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14–26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible.ConclusionWe were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence.

Blocking Fas Ligand on Leukocytes Attenuates Kidney Ischemia-Reperfusion Injury

Inflammation contributes to the pathogenesis of ischemic acute kidney injury (AKI), and T cells mediate the early phase of ischemia-reperfusion injury (IRI). The Fas/Fas ligand (FasL) pathway modulates the balance of T cell subsets in the peripheral circulation as well as multiple inflammatory responses, suggesting that FasL may mediate ischemic AKI. Here, we induced bilateral renal IRI in mice bearing a loss-of-function mutation of FasL (the gld mutation) and in wild-type mice. Compared with wild-type mice, serum creatinine was lower in gld mice (1.4 ± 0.9 mg/dl versus 2.6 ± 0.4) at 24 hours after IRI (P<0.05). In addition, gld mice had fewer TNF-α-producing T lymphocytes in the kidneys and renal lymph nodes. Furthermore, pharmacologic blockade of FasL protected the kidneys of wild-type mice from IRI. Analysis of bone marrow chimeric mice suggested that the pathogenic effect of FasL involves leukocytes; reconstitution of wild-type mice with gld splenocytes attenuated IRI. In contrast, reconstitution of gld mice with wild-type splenocytes enhanced IRI. These data demonstrate that FasL, particularly on leukocytes, mediates ischemic AKI.

Host Response to Porcine Strains of Escherichia coli in a Novel Pyelonephritis Model

The initial pathology and pathogenesis of pyelonephritis and the influence of different strains of Escherichia coli were investigated in a novel porcine model. Nine female pigs were divided into three groups (A, B and C) and inoculated repeatedly into one renal pelvis with porcine pyelonephritis E. coli strain LK67 (P fimbriae PapG(I)), LK76 (type 1 fimbriae) or LK82 (type 1 fimbriae and P fimbriae PapG(II/III)), respectively. The contralateral kidneys were inoculated with saline and served as controls. Pigs were killed 6h post-inoculation (hpi). Differential leucocyte counts, serum biochemical analyses and measurement of serum concentrations of proinflammatory cytokines and acute phase proteins were carried out at 0, 3 and 6 hpi. Bacteriological evaluation of urine, kidneys, spleen, liver, abdominal swabs and blood samples and gross and histopathological evaluation of kidneys, renal lymph nodes, liver and spleen were performed by quantitative, semiquantitative and/or descriptive methods. Immunohistochemistry was used to identify cells expressing L1 antigen, CD3ɛ, CD4, CD8, CD79αcy and lysozyme, and to identify E. coli and Tamm-Horsfall protein (THP). E. coli was re-isolated from all inoculated kidneys. Gross and microscopical lesions of acute pyelonephritis were demonstrated in all but one kidney inoculated with E. coli, but in none of the control kidneys. Renal parenchymal infiltration with both neutrophils and mononuclear cells, primarily CD3+ T lymphocytes, was observed at 6 hpi. Most T lymphocytes were CD8+. Pigs in group C had the highest mean pathology scores. Neutrophils were the dominant renal leucocyte in this group, while the number of mononuclear cells was at least equal to the number of neutrophils in the lesions of pigs from groups A and B. Kidneys with a high number of E. coli had severe lesions. Systemic spread of E. coli was observed in five pigs. THP was observed interstitially in 89% of the E. coli-inoculated kidneys. In all groups, increased numbers of neutrophils and decreased numbers of lymphocytes and monocytes were shown by differential leucocyte count at 6 hpi, and from 3 to 6 hpi there was a significant increase in C-reactive protein concentration.

Reassessment of Renal Cell Carcinoma Lymph Node Staging: Analysis of Patterns of Progression

To evaluate the prognostic value of lymph node (LN) metastasis and the therapeutic role of LN dissection (LND) in patients with renal cell carcinoma. We reviewed the medical records of 1503 patients who had undergone nephrectomy from 1990 to 2007. The patients were stratified according to the number, location, and size of LN metastases. The disease-free survival, cancer-specific survival, and survival relative to the preoperative suspicion of LN metastasis were analyzed. Of the 1503 patients, 726 (48.3%) had Stage pN0, 37 (2.5%) had Stage pN+, including 16 with pN1 and 21 with pN2, and 740 (49.2%) had Stage pNx. The average number of LNs removed was 5 (range 1-33), and the average size of the metastasized LNs was 2.4 cm (range 0.8-6). Of the patients without preoperative clinical evidence of LN metastasis, 203 underwent LND; all had Stage pN0. The LN stage was a significant predictor of distant metastasis-free survival (P = .002) and cancer-specific survival (P = .001) between the pNx/pN0 and pN+ groups but not between the pN1 and pN2 groups. Metastasized LN size (<3 vs ≥3 cm) also significantly predicted for distant metastasis-free survival (P = .003) and cancer-specific survival (P = .001). In LN-positive patients, LND improved local recurrence-free survival but not distant metastasis-free survival or cancer-specific survival. The current LN staging system, which is dependent on the number of metastatic LNs, did not significantly correlate with the prognosis in patients with renal cell carcinoma. In contrast, LN size (<3 vs ≥3 cm) better reflected the effect of this disease on survival. The therapeutic role of LND might be limited.

Role of T cell mediated inflammation in lupus-like glomerulonephritis (GN) (93.40)

Abstract Renal involvement in lupus is characterized by glomerular immune complexes, acute proliferative GN and progressive renal failure. To investigate the pathogenic role of T cells in renal lupus, an antigen-specific model of GN was established. A novel, anti-α8 integrin immunoliposomal delivery system (α8ILs) was designed for targeted delivery to the renal glomerulus. Ovalbumin loaded α8ILs (ova-α8ILs) were injected i.v. into C57BL/6 mice leading to a rapid delivery of ova in the glomerular mesangium. Injection of ova-α8ILs followed by ova-reactive transgenic OT2 cells activated in vitro, resulted in GN. On day 7 after injection, the renal cortex showed T cell, macrophage and dendritic cell infiltration. To mimic lupus GN, mice were injected with ova-α8ILs and mouse anti-ova serum forming glomerular immune complexes. This was followed by injection of naïve CSFE labeled OT2 cells. Two days after cell transfer, mice with glomerular immune complexes showed dividing OT2 cells preferentially in renal lymph nodes compared to mice given ova-α8ILs alone. Recently, macrophage infiltration into the renal interstitium has been identified as the harbinger of renal failure. Our data suggest that glomerular antigen-specific T cell infiltration may be sufficient for recruitment of macrophages into the renal cortex and the onset of progressive renal inflammation. In addition, glomerular immune complexes lead to a rapid, local activation of glomerular antigen reactive T cells.

Preoperative induction with sorafenib pathologically downstaged advanced renal cell carcinoma: A case report

We present the case of a patient with renal cell carcinoma treated preoperatively with sorafenib. Complete resection of the left renal mass measuring 7.2 x 6.6 cm seemed to be difficult at diagnosis because of large renal hilar lymph nodes. With a short period of sorafenib administration, marked shrinkage of the renal mass and lymphadenopathy was observed after the patient experienced fulminant hepatic failure and a severe hand-foot skin reaction. Two-dimensional computed tomography revealed 60%, 78% and 84% reduction in the primary renal tumor, lung metastatic nodules and lymph nodes, respectively. Tumor shrinkage allowed for complete resection of the left kidney and the lymphadenopathy. Pathological findings revealed that over 90% of the renal tumor was substituted by necrotic fibrotic tissue and that the residual neoplastic component was diagnosed as clear cell carcinoma. The lymph nodes that were resected were negative for malignancy. At 6 months after radical nephrectomy, a new computed tomography scan revealed no evidence of disease with the disappearance of lung nodules.

Diagnosis and treatment of carcinoma of renal pelvis accompanied with kidney stones

Objective To discuss the diagnosis and treatment of carcinoma of renal pelvis ac-companied with kidney stones. Methods Twenty-one cases of carcinoma of renal pelvis with kidney stones were reviewed. The urinary stones history was from 10 d to 24 years with an average of 27 months. Four cases had recurrent fever, weight loss. Seventeen cases had gross hematuria. CT scan-ning was performed in 17 cases, which indicated 9 cases of carcinoma of renal pelvis, 4 cases of possi-ble renal mass and enlarged renal hilum lymph nodes. MRU was performed in 10 cases, which showed 9 cases of stones concomitant with carcinoma of renal pelvis. IVU indicated 13 cases of light filling of contrast and 8 cases of complete negative filling. Nine cases who had been diagnosed before surgery were performed radical nephrectomy and local lymph nodes dissection. Five cases were carried out ne-phrostomy first because of pyonephrosis, then secondary subcapsule nephrectomy was performed, 2 of them who were diagnosed with carcinoma of renal pelvis after surgery were performed with ureterecto-my and excision of bladder cuff. Three cases were performed with subcapsule nephrectomy because of dense perinephric adhesion. Three cases with complicated calculi and nonfunctional kidney were per-formed with nephroureterectomy, 2 of them who were diagnosed with carcinoma of renal pelvis were carried out with ureterectomy and excision of bladder cuff. One case who was performed PCNL under ultrasound guidance was found a mass in the renal pelvis. The pathological examination indicated ade-nocarcinoma. Radical nephrectomy and lymphadenectomy of renal hilum were performed afterwards. Resnlts Twenty-one cases were performed with pathological examination, in which there were 4 ca-ses of transitional cell carcinoma, 16 cases of squamous cell carcinoma and 1 case of adenocarcinoma. All the 21 cases were discharged after surgery. Nine of them were followed up with 4 to 28 months. Six cases were dead. The post-surgery survival time was 3 to 21 months. Two of them died of heart infarction, 4 died of metastasis. Conclusions The carcinoma of renal pelvis should be considered be-fore surgery in the patients with long history of renal calculi, hydronephrosis and infection. CT scan-ning and MRU are helpful for the diagnoses of renal calculi concomitant with carcinoma of renal pel-vis. Earlier diagnosis, earlier management of renal calculi can extend survival time of the patients with renal calculi concomitant with carcinoma of renal pelvis. Key words: Kidney calculi; Carcinoma; Kidney pelvis

Fluorescence Lymph Node Mapping in Living Mice Using Quantum Dots and a Compression Technique

The lymphatic system is essential in oncology and immunology, and in vivo fluorescence imaging plays a major role in assessing the lymphatic drainage. We investigated non-invasive fluorescence lymph node mapping in mice with special reference to the assessment of deep abdominal lymph nodes. Quantum dots were injected subcutaneously into the rear footpads of mice, and the time course of the fluorescent signal was assessed. Visualization of abdominal lymph nodes was compared with and without compression of the abdomen with transparent, colorless tape at injection doses of 1, 5, and 20 pmol. Popliteal, sacral, iliac, and renal lymph nodes were delineated by non-invasive imaging. Lymph node signals increased up to 3 h after injection. Compression of the abdomen markedly improved the visualization of the iliac nodes, which were invisible at 5 pmol without compression and visible at 1 pmol with compression. Fluorescence lymph node mapping using quantum dots allowed the visualization of deep abdominal lymph nodes in addition to superficial nodes in intact mice, with the aid of a simple compression technique.

Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.

Deficiency of Type I IFN Receptor in Lupus-Prone New Zealand Mixed 2328 Mice Decreases Dendritic Cell Numbers and Activation and Protects from Disease

Type I IFNs are potent regulators of innate and adaptive immunity and are implicated in the pathogenesis of systemic lupus erythematosus. Here we report that clinical and pathological lupus nephritis and serum anti-nuclear Ab levels are greatly attenuated in New Zealand Mixed (NZM) 2328 mice deficient in type I IFN receptors (IFNAR). To determine whether the inflammatory environment in NZM 2328 mice leads to IFNAR-regulated changes in dendritic cells (DC), the number, activation, and function of DC subsets were compared in 2- and 5-mo-old (clinically healthy) female NZM and NZM-IFNAR(-/-) mice. Numbers of activated CD40(high) plasmacytoid DC (pDC) were significantly increased in renal lymph nodes of 2-mo-old NZM but not NZM-IFNAR(-/-) mice, suggesting an early IFNAR-dependent expansion and activation of pDC at disease sites. Relative to NZM spleens, NZM-IFNAR(-/-) spleens in 5-mo-old mice were significantly decreased in size and contained reduced numbers of conventional DC subsets, but not pDC. Splenic and renal lymph node NZM-IFNAR(-/-) DC analyzed directly ex vivo expressed significantly less CD40, CD86, and PDL1 than did NZM DC. Upon activation with synthetic TLR9 ligands in vitro, splenic NZM-IFNAR(-/-) DC produced less IL-12p40/70 and TNF-alpha than did NZM DC. The limited IFNAR(-/-) DC response to endogenous activating stimuli correlated with reduced numbers of splenic activated memory CD4(+) T cells and CD19(+) B cells in older mice. Thus, IFNAR signaling significantly increases DC numbers, acquisition of Ag presentation competence, and proinflammatory function before onset of clinically apparent lupus disease.

A Multi-Institutional Study on the Safety and Efficacy of Specimen Morcellation After Laparoscopic Radical Nephrectomy for Clinical Stage T1 or T2 Renal Cell Carcinoma

Specimen morcellation during laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) is controversial. We seek to evaluate the safety and efficacy of specimen morcellation and LRN for treatment of presumed malignant renal lesions. We retrospectively reviewed all patients who underwent LRN at three academic institutions from 1996 to 2007. One hundred eighty-eight patients underwent specimen morcellation after LRN for enhancing solid or cystic renal masses. LRN was successfully performed on all the patients. Patient age ranged from 36 to 94. One hundred sixty-seven patients were in clinical stage T1, 19 patients T2, and unknown in two. The specimen was manually morcellated within a Cook Lap Sac or Endocatch II bag under laparoscopic or direct observation. On histological review of morcellated specimens, 165 patients were confirmed to have RCC, 17 had an oncocytoma, and 2 had benign cysts. At least 13 patients with RCC were pathologically upgraded to stage T3. Mean operative time was 225 minutes (range 94-650). Mean hospital stay was 2.5 days (range 1-8). In patients with RCC, 11 developed recurrent disease with mean follow-up of 21 months (range 0.3-111). In one patient, a port site recurrence occurred in concert with renal fossa and lymph node metastases. Intracorporeal mechanical morcellation after LRN appears to be safe and effective in clinical stage T1 and T2 RCC. This supports the use of morcellation as an alternative for intact specimen removal in properly selected patients.

Supraclavicular lymph node metastases of unknown origin: HPV-typing identifies the primary tumour

Cancers of unknown primary origin (CUP) account for 0.5-10% of all malignancies. CUP patients with metastases have a median survival of approximately 6 months, despite therapy. Identification of the primary tumour site may offer the opportunity of a specific and more efficient treatment. The case of a 45-year-old woman with supraclavicular lymph node metastases of a squamous cell CUP is reported. A staging laparoscopy with multiple biopsies and a loop diathermy excision of the cervix were performed. Human papillomavirus (HPV)-testing in the tissues revealed the tumour cells as metastases of an occult cervical cancer. Primary platin-based chemotherapy combined with paclitaxel leads to a complete apparative remission. Twelve months later, staging positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in combination with computed tomography identified an isolated left renal lymph node metastasis. The patient received targeted radiation therapy, combined with cisplatin. To date, 19 months after diagnosis, she is doing well without any evidence of disease. The presented case report addresses the difficulties involving the identification of CUP. HPV-DNA is found in over 95% of cervical cancers. As the presented case illustrates, testing for this virus DNA in human tissues can be a useful diagnostic tool in patients with CUP where cervical cancer is the possible primary tumour.

Cytology of metastatic renal medullary carcinoma in pleural effusion: A study of two cases

Renal medullary carcinoma (RMC) is a rare and aggressive malignant epithelial neoplasm of the kidney. It almost exclusively affects children and young adults with a sickle cell trait or sickle cell disease. The majority of RMC patients present with widely disseminated disease at the time of diagnosis. Herein, we report two cases of young African-American patients with history of sickle cell trait, hematuria and renal mass, who present with malignant right pleural effusions. The cytology of pleural effusion reveals predominantly clusters and individual tumor cells. The tumor cells show high nuclear to cytoplasmic (NC) ratios and large nuclei with nuclear pleomorphism, nuclear grooves, and prominent single or multiple nucleoli. The cytoplasm is dense with a vacuolated and two-tone appearance. Surgical specimens of renal mass and lymph node show features of RMC. Metastatic RMC to the serous cavity is rare and may present a diagnostic dilemma since it may mimic a poorly differentiated adenocarcinoma or other high-grade malignant neoplasms. RMC should be considered in the differential diagnosis in young patients with a renal mass, particularly in those with history of sickle cell trait or sickle cell disease.

Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury

The progression of kidney disease to renal failure correlates with infiltration of mononuclear immune cells into the tubulointerstitium. These infiltrates contain macrophages, DCs, and T cells, but the role of each cell type in disease progression is unclear. To investigate the underlying immune mechanisms, we generated transgenic mice that selectively expressed the model antigens ovalbumin and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin-specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in periglomerular mononuclear infiltrates and inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. Repetitive T cell injections aggravated infiltration and caused progression to structural and functional kidney damage after 4 weeks. Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross-presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for CTL activation in the lymph nodes and for simultaneous presentation to Th cells by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and macrophages. The importance of DCs was established by the fact that DC depletion rapidly resolved established kidney immunopathology. These findings demonstrate that glomerular antigen-specific CTLs and Th cells can jointly induce renal immunopathology and identify kidney DCs as a mechanistic link between glomerular injury and the progression of kidney disease.

Primary Thyroid-like Follicular Carcinoma of the Kidney

Thyroidization of kidney reminiscent of thyroid follicles with accumulation of inspissated colloid-like material in renal tubules is a hallmark of chronic pyelonephritis. We identified 6 tumors in the kidney, distinct from currently known subtypes of renal cell carcinoma, with a striking histology that closely mimicked well-differentiated thyroid follicular neoplasms and raised the possibility of metastatic follicular thyroid carcinoma. Three occurred in males and 3 in females with an age range of 29 to 83 years and size range from 1.9 to 4 cm. All tumors were encapsulated and exclusively demonstrated follicular architecture comprising of microfollicles and macrofollicles containing inspissated colloid-like material. A minor component of small tightly packed follicles devoid of secretions was also noted. The follicles were lined by cells with moderate amphophilic to eosinophilic cytoplasm with round nuclei and occasional prominent nucleoli. The tumors were nonimmunoreactive with thyroglobulin and thyroid transcription factor 1 and for markers contemporarily used for renal differentiation. The tumors had a gene expression profile distinct from clear cell and chromophobe renal cell carcinoma. Comparative genetic hybridization failed to reveal cytogenetic alterations. Mean follow-up of 47.3 months (range: 7 to 84 mo) showed that 5 patients had no evidence of disease and 1 developed a metastasis to the renal hilar lymph nodes in which the follicular architecture with colloid was retained. Thyroid-like follicular renal cell carcinoma represents a unique histologic subtype of renal cell carcinoma of low malignant potential and its primary importance is to distinguish it from metastatic carcinoma from the thyroid.

Increased cell proliferation in spleen and lymph nodes peripheral to contact allergen application site

The local lymph node assay (LLNA) is widely used to identify chemicals that are contact sensitizers. The assay involves dosing mice with the chemical on both ears and pooling the superficial parotid lymph nodes for assessment of lymphocyte proliferation as a marker of sensitization. The present study explored potential reduction in animal usage by dosing one ear with the allergen and the other with vehicle-only. The respective draining lymph nodes were processed separately for tritiated thymidine ( 3H-TdR) incorporation. Cell proliferation in proper axillary and renal nodes, as well as in the spleen was also assessed. Cross-contamination of the chemicals from the dosed ears to other parts of the body via preening was prevented by dosing restrained animals and washing off the residual chemical with saline after 4 h. Dosing the left ear with 0.02% oxazolone (OX) on unrestrained animals resulted in marked cell proliferation in its draining lymph node (stimulation index, SI = 12.8) and in the lymph node draining the contra-lateral vehicle-dosed ear (SI = 6), as well as the proper axillary lymph nodes (SI = 3.3). Increased 3H-TdR incorporation was not observed in the renal lymph nodes (SI = 1.1). Similar stimulation of cells was observed in the lymph node draining the ear contra-lateral to the 30% hexylcinnamaldehyde (HCA)-dosed ear. Increased proliferative activity was observed in contra-lateral draining lymph nodes of restrained mice demonstrating that these results cannot be attributed to cross-contamination of adjacent skin. A significant increase in proliferation of splenocytes was also observed. It is concluded that dermal application of a contact allergen, as exemplified by OX and HCA, may induce cell proliferation in the neighboring lymph nodes and spleen indicative of hapten and/or haptenated proteins diffusing through the skin to peripheral nodes and the blood to produce systemic sensitization. It is also possible that lymphatic capillaries may communicate between the left and right side of the mouse head. Thus the contra-lateral draining superficial parotid node cannot be used as a control for application of contact allergen to a single ear in a modified LLNA.