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The value of histochemical analysis in the diagnosis of medical renal diseases has long been known, and its use continues currently. Depending on the particular disorder in question, a variety of "special" stains may be applied to renal biopsies. These include the periodic acid-Schiff, Masson trichrome, Jones, von Kossa, Verhoeff-van Gieson, Congo Red, and toluidine blue methods, among others. This review considers the application of such techniques in the assessment of vascular, glomerular, and tubulointerstitial lesions of the kidney.

Background Although the majority of post-transplant lymphoproliferative disorder (PTLD) cases are associated with Epstein–Barr virus (EBV), 20–42% of cases are EBV negative (EBV-N). The antigenic stimulus that drives EBV-N PTLD is unknown, but is likely heterogeneous. A common feature of PTLD, regardless of EBV status, is an abnormal polytypic lymphoplasmacytic infiltrate. Immunglobulin-G4 (IgG4) syndrome is also characterized by a polytypic lymphoplasmacytic infiltrate with a predominance of IgG4-positive (IgG4-P) plasma cells. Methods We investigated the possibility of an association between EBV-N PTLD and IgG4 syndrome. Of 33 evaluated PTLD cases, 9 (27%) were EBV-N. EBV-N PTLD cases showed longer transplantation-to-diagnosis times than EBV-positive cases. Results A single patient had a preceding benign duodenal biopsy with focally prominent IgG4-P plasma cells; however, no clinical data supported IgG4 syndrome, precluding an association between IgG4 syndrome and subsequent EBV-N PTLD in this patient. Conclusion As none of 29 evaluable cases of PTLD (including all 9 EBV-N cases) were associated with an increase in IgG4-P plasma cells, IgG4 syndrome does not appear to play a role in the etiology of EBV-N PTLD. The significance of these findings and the current understanding of the etiology of EBV-N PTLD are discussed.

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and 'hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma.

Educational evolution is particularly important in pathology, particularly cytopathology, due to the vast amounts of independent learning required to master this field. In this study, learning challenges faced by pathology residents were addressed through a variety of educational modalities including 24 short (∼10 minute) online tutorials (dubbed "Sound Bites") covering selected topics in cytopathology as well as other areas of anatomic and clinical pathology. Additionally, residents were provided with an annotated glass slide set covering pediatric pathology with an associated multiple choice self-assessment as well as multiheaded microscope slide review sessions. Use of these modalities was tracked and residents surveyed about their experiences using them. All 20 residents (100%) reported using Sound Bites either from work computers, home computers, or mobile devices. Residents reported that easy accessibility, brevity, and opportunities for self-assessment were important variables contributing to this use, and that Sound Bite use would make them more likely to benefit from in-person teaching through lectures and/or slide sessions. Within 12 months of the release of the first Sound Bite, individual Sound Bites were accessed a total of 1169 times (mean: 49 times per Sound Bite). In contrast, slide sets were only accessed about once a month and were only employed by 30% of residents (6 of 20) for independent study; only 20% (4 of 20) completed the accompanying multiple choice self-assessment. All residents attended multiheaded microscope slide review sessions. Whereas traditional educational methods remain valuable tools in pathology education, these data suggest that short, web-based tutorials represent a valuable adjuvant teaching tool.

Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers, we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation, and the longitudinal validation studies for noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time points after kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early after kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients.

The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia.

The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a Z65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus, "the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in

The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

Antiglomerular basement membrane (anti-GBM) antibodies are more often accompanied by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) than by proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA). Both disease processes can affect the kidneys and/or the lungs. Patients with dual positive disease may have an atypical presentation which may delay diagnosis and treatment. Here we report a case of crescentic glomerulonephritis associated with positive PR3-ANCA and anti-GBM antibodies who underwent both lung and kidney biopsies.

Weber-Christian disease (W-CD) is associated with relapsing nodular panniculitis and a variety of systemic findings. Renal parenchymal involvement has been rarely reported. The authors describe a case of nephrotic syndrome in an African-American man with a W-CD flare. The patient had chills and low-grade fever with painful lower extremity skin lesions. A renal biopsy demonstrated the tip variant of focal segmental glomerulosclerosis (FSGS). The kidney biopsy also suggested parenchymal involvement by W-CD disease, with supportive ultrastructural findings. The synchronous W-CD flare and biopsy-proven FSGS and the rapid and sustained response of both to limited treatment suggest a causative association.

Tumor-to-tumor metastasis (TTM) is a rare phenomenon where a focus of distinct metastatic disease is discovered with a second primary tumor. Although renal cell carcinoma is the most frequent recipient of metastatic tumor cells, oncocytomas have also previously been described. We present the case of a patient with incidentally detected mammary adenocarcinoma within an oncocytoma 16 years following primary treatment. The mass was treated with partial nephrectomy, with the surgical pathology specimen showing clear delineation of the pleomorphic lobular carcinoma and oncocytoma cells.

Fabry disease is an X-linked recessive lysosomal storage disease caused by a deficiency of α-galactosidase A, with characteristic ultrastructural cytoplasmic myelin-like inclusions. Renal lesions are seen in male and variably in heterozygous female patients. One previous report has described Fabry disease involving a renal allograft from a deceased female donor with no history of Fabry disease. The authors describe another case, in which suspicion for Fabry disease was raised ultrastructurally. This serves as a reminder that proteinuria after renal transplantation may be due to donor-derived disease. Fabry disease is probably an underrecognized cause of graft dysfunction. This case provides further justification for ultrastructural examination of renal allograft biopsies.

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD.

Sinonasal adenocarcinomas (SNACs) are uncommon malignancies that show a variety of growth patterns. These lesions are classified as intestinal or nonintestinal, the latter subclassified as low grade or high grade. We have noted that some low-grade nonintestinal SNACs are associated with respiratory epithelial adenomatoid hamartomas (REAHs), also rare lesions that have recently been shown to be neoplastic. We reviewed 29 nonintestinal low-grade SNACs seen at our institution over a 20-year period, with particular attention to morphology and concomitant REAHs. Nine (31%) low-grade SNACs demonstrated a predominantly exophytic and papillary growth pattern, and 18 (72%) had a more tubular growth pattern. Two (7%) were categorized as "other." Six low-grade tubular SNACs were associated with REAHs. An immunohistochemical panel was performed on 2 of these cases; neoplastic cells were immunoreactive with antibodies to CK7 and S100 protein and nonreactive with antibodies to CK20, similar to other low-grade SNACs. No basal cells or myoepithelial differentiation was seen with immunohistochemical stains for p63 and 34betaE12. This association of low-grade tubular SNACs with REAHs suggests that REAHs may be related to some adenocarcinomas.

Three cases of cutaneous pseudosarcomatous polyp, a lesion recently described in the dermatopathology literature, are reported here. These benign proliferations display dramatic cytologic pleomorphism, but despite their disquieting morphological features, they have behaved in a benign fashion to date. All 3 lesions in this study were clinically innocuous, with 1 having been present for 1 year and another for 2 years. The first lesion arose on the back of a 30-year-old man, the second on the nasal columella of a 65-year-old woman, and the third on the back of a 91-year-old woman. All 3 had the typical architecture of a fibroepithelial polyp (acrochordon) with widely separated stellate cells occupying a myxoid to collagenous stroma. Markedly pleomorphic stellate cells were widely dispersed, with an increased density of atypical cells beneath the epidermis and in small foci of adipose tissue in 1 case. Multinucleated cells, some with a floret-type configuration, were also observed. One of the polyps demonstrated focal mild hyalinization of vessel walls. Only rare mitotic figures were identified in 2 cases, but 1 showed atypical forms. Immunohistochemically, the atypical cells reacted diffusely for vimentin and variably for CD34 and factor XIIIa, but they lacked smooth muscle actin and desmin. Cutaneous pseudosarcomatous polyps can be added to the list of pathologic entities with symplastic or pseudomalignant features.

Immunohistochemistry using a broad panel of markers is an invaluable tool for diagnosing sarcomatoid mesothelioma. Membranous podoplanin staining has been proposed as a specific and sensitive marker to distinguish epithelioid mesothelioma from adenocarcinoma. We found that cytoplasmic podoplanin staining was present in sarcomatoid mesotheliomas, and wanted to explore the reproducibility and specificity of this staining pattern. Immunohistochemistry for podoplanin, using 2 podoplanin antibodies (antipodoplanin and D2-40), was performed in 55 mesotheliomas (24 epithelioid, 18 sarcomatoid, and 13 biphasic), 80 pulmonary adenocarcinomas, 8 synovial sarcomas, and 16 sarcomatoid carcinomas. Expression of calretinin, vimentin, MOC31, and TTF-1 was also examined in all adenocarcinomas, sarcomatoid carcinomas, 7 synovial sarcomas, and 21 of the mesotheliomas. Calretinin staining performed previously on an additional 31 mesotheliomas was reviewed. Using membranous or cytoplasmic staining as indicative of positivity, we found that antipodoplanin and D2-40 each stained 84% of mesotheliomas (antipodoplanin: 46/55; D2-40: 38/44), including 72% of sarcomatoid mesotheliomas (antipodoplanin: 13/18; D2-40: 11/14). With antipodoplanin antibody, no staining was seen in the pulmonary adenocarcinomas (0/80, 0%) or the synovial sarcomas (0/8, 0%), and weak cytoplasmic staining was seen in only 1 sarcomatoid carcinoma (1/15, 7%). D2-40 showed similar results, staining 3% (2/80) of pulmonary adenocarcinomas, 13% (1/8) of synovial sarcomas, and 8% (1/13) of sarcomatoid carcinomas. Overall sensitivities and specificities were 84% and 99% for antipodoplanin, and 86% and 96% for D2-40. These findings suggest that cytoplasmic podoplanin expression may be useful in the diagnosis of sarcomatoid mesothelioma, although it should be used with caution on biopsy material.

Endometrial stromal sarcomas are uncommon tumors of the uterus, and the cytologic features have only been reported in a number of case reports that mostly discuss the features of higher grade undifferentiated sarcomas. This article discusses the cytologic features of a large series of low-grade endometrial stromal sarcomas (ESSs) sampled by a variety of methods. We reviewed our histologic files for all confirmed cases of low-grade ESS, and followed this by a computerized search for any corresponding cytologic specimens. We identified 12 Papanicolaou tests and 9 nongynecologic specimens. Most cases showed moderate to marked cellularity with a combination of single cells and stromal fragments. Blood vessels, interspersed between the clusters of stromal cells, were seen in 15 cases; 4 of these had supporting hyaline matrix. The cells were predominantly spindle shaped with scant to moderate cytoplasm, round to ovoid nuclei, and fine chromatin. Mitotic figures and nucleoli were rare. Most cases had a clean background.

Renal involvement by a malignant infiltrative process is often suspected in patients with bilaterally enlarged kidneys and concurrent malignancies. Acute renal failure (ARF) can rarely occur secondary to such an infiltrative process. We present 2 cases in which ARF is attributable to malignant hematolymphoid infiltration. The first case involves diffuse, bilateral involvement of the kidneys by non-Hodgkin's lymphoma. The patient's renal function improved dramatically after the initiation of chemotherapy, clearly linking the development of ARF to the malignant process. In the second case, infiltration of the kidneys by plasma cell leukemia resulted in dialysis dependence. To our knowledge, this represents the first reported case of ARF attributable to documented renal infiltration by plasma cell leukemia. A review of the potential causes of renal failure in hematolymphoid malignancy, focusing on the direct impact of the infiltrative process and on the spectrum of renal disease in plasma cell dyscrasia, is presented.

Calretinin has been proposed as a novel marker of ovarian sex cord-stromal tumors (SCST); this study aims to determine whether calretinin can complement or supplant the established utility of inhibin in the differential diagnosis of SCST. WT1 has been shown to be expressed in ovarian serous, but not mucinous neoplasms; its expression in a variety of ovarian tumors is also examined. Formalin-fixed, paraffin-embedded archival tissues from 111 primary ovarian tumors were analyzed with commercially available antibodies using semi-automated immunohistochemistry. Results were graded on a 4-tiered scale with staining of more than 0 but less than 5% of cells considered focal. Of 27 SCST, 56% were calretinin and 56% inhibin positive overall; 90% of granulosa cell tumors, 57% of Sertoli-Leydig cell tumors, 33% of thecomas, and 14% of fibromas were calretinin positive. Inhibin was expressed in 60% of granulosa cell tumors, 71% of Sertoli-Leydig cell tumors, 43% of fibromas, and 33% of thecomas. Of 35 surface epithelial tumors (SET), 8% of serous papillary tumors were calretinin positive, whereas 8% of serous papillary tumors and 13% of poorly differentiated carcinomas expressed inhibin. WT1 was expressed in 29% of all endometrioid carcinomas, 10% of borderline mucinous tumors, and no mucinous carcinomas; however, most of the other SETs were positive (77% serous papillary and 88% poorly differentiated carcinomas). Among the SCST, WT1 stained only granulosa cell tumors (75%), though often weakly or variably. Calretinin has only slightly greater sensitivity (76% versus 65%) and equal specificity to inhibin (92%) in the differential staining of granulosa or Sertoli-Leydig cell tumors, that is, nonstromal SCST. Hence, calretinin cannot replace but could complement inhibin as part of an immunohistochemical panel used for diagnostically challenging SCST. Although WT1 should be reliably positive in non-mucinous SET, staining of granulosa cell tumors and lack of expression in a sizable subset of endometrioid carcinomas may confound interpretation.

Nonsalivary sinonasal adenocarcinomas can be divided into low-grade and high-grade tumors. The former are often papillary and the latter are usually of intestinal type, morphologically similar to metastatic colonic carcinoma. Antibodies to CDX2, a transcription factor gene highly specific for intestinal adenocarcinomas, MUC2, a mucin gene expressed in adenocarcinomas from various sites, and cytokeratins (CK) 7 and 20 were used to examine the two groups of tumors. Formalin-fixed, paraffin-embedded tissue from 22 sinonasal adenocarcinomas was reclassified into 9 high-grade intestinal-type, 3 high-grade nonintestinal, and 10 low-grade, predominantly papillary adenocarcinomas. Immunohistochemical staining was graded on a 0 to 4+ scale with 5% or greater tumor cell staining considered positive. Of the high-grade intestinal group, 78% demonstrated 4+ CDX2 positivity, with 44% MUC2 positive. Although 89% of this group was CK7 positive, the percent of staining was variable. A majority (67%) of the intestinal cases was 4+ CK20 positive. Almost every nonintestinal adenocarcinoma (90%) (low- and high-grade) was CK7 positive (7 of 9, 4+), without expression of any of the three colonic adenocarcinoma markers. The three high-grade nonintestinal tumors had the expression profile of the low-grade papillary group with the exception of focal MUC2 positivity in 1 case. Intestinal-type adenocarcinomas have an expression profile distinct from nonintestinal sinonasal adenocarcinomas. The former are similar, but not identical, to colonic adenocarcinomas. Immunohistochemical staining for CDX2, MUC2, and differential cytokeratins does not differentiate metastatic colorectal from primary sinonasal intestinal-type adenocarcinoma.

The 40-kilodalton processed glycoprotein, mesothelin, is highly expressed in epithelial mesotheliomas and adenocarcinomas of the ovary (serous papillary) and pancreas, but its expression in a large series of other common carcinomas has not been completely explored. In the present study, we used oligonucleotide and tissue microarrays to profile the expression of the mesothelin gene (MSLN) and encoded protein, respectively. Among 150 carcinomas of multiple anatomic sites, we found the highest average expression of MSLN in serous carcinomas of the ovary and adenocarcinomas of the pancreas, consistent with previous reports, as well as measurable but less-striking expression in pulmonary, gastric/esophageal, and colorectal adenocarcinomas. On tissue microarrays containing 621 carcinomas derived from the same and additional sites as those profiled by gene expression, mesothelin immunoreactivity was highest in cancers of the ovary (serous papillary, endometrioid, and undifferentiated) and pancreas, with less frequent staining seen in adenocarcinomas of the endometrium, lung, and stomach/esophagus. Some immunopositivity was observed in 42% of pulmonary adenocarcinomas, including 18% that had >50% of tumor cells that were immunoreactive. Some 14% of breast and 30% of colorectal adenocarcinomas showed immunopositivity, but no case contained >50% tumor cells that were immunoreactive. Mesothelin was either entirely absent or present in

To further delineate specific staining patterns and refine the differential usefulness of cytokeratin (CK) 7/20 staining, we studied multiple ovarian tumors and primary nongynecologic neoplasms likely to metastasize to the ovary. Immunohistochemical analysis with semiquantitative grading to give quartile scores (0-4) was performed on 127 cases. Subsequent analysis indicated that a more informative diagnostic segregation could be achieved with a biphasic grading system (>50% staining, positive; 50% or less, negative). Lower intestinal tumors were CK7- and usually CK20+, while upper gastrointestinal tumors, including those of pancreatobiliary origin, were mostly CK7+ and CK20-. Serous papillary ovarian tumors were all CK7+ and CK20-. Mucinous ovarian carcinomas were all CK7+ and slightly more often CK20-, whereas the small number of ovarian borderline mucinous tumors studied were the most problematic, with no clear pattern. Multiple different tumor types from all nonovarian gynecologic sites were fairly consistently CK7+ and almost always CK20-. Differential CK staining of mucinous tumors of the female genital tract using CK7 and CK20 is useful for predicting the site of origin, provided samples are adequate in size. The most specific usefulness is the identification of lower gastrointestinal vs "other" neoplasms.

Penile squamous cell carcinoma (SCC) is sometimes an aggressive disease that has a variable worldwide incidence, in part due to differing rates of inflammatory and infectious risk factors. In the developed world, penile SCC is a rare malignancy, and most studies therefore originate in less developed countries. The current study was undertaken to examine the morphologic and immunohistochemical features of penile SCC from a region with low disease incidence. Sixty-two complete or partial penectomy specimens from 59 patients were reviewed. Twenty-six patients had metastasis, 3 had recurrent disease, and 7 were dead due to tumor. Most patients were uncircumcised (72%). Twenty-two percent of carcinomas were associated with lichen sclerosis. Perineural invasion was significantly associated with metastasis (P=0.007). Most SCCs (65%) had the usual keratinizing morphology, and these tumors were significantly associated with the differentiated form of intraepithelial lesion (P

The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated by: (1) identifying specific CNIT molecular pathways that associate with allograft injury (cross-sectional study) and (2) assessing the contribution of the identified CNIT signature in the progression to CAD with IF/TA (longitudinal study). Kidney biopsies from well-selected transplant recipients with histological diagnosis of CNIT (n = 14), acute rejection (n = 13) and CAD with IF/TA (n = 10) were evaluated. Normal allografts (n = 18) were used as controls. To test CNIT contribution to CAD progression, an independent set of biopsies (n = 122) from 61 KT patients collected at 3 and ~12 months post-KT (range = 9-18) were evaluated. Patients were classified based on 2-year post-KT graft function and histological findings as progressors (n = 30) or nonprogressors to CAD (n = 31). Molecular signatures characterizing CNIT samples were identified. Patients classified as progressors showed an overlap of 7% and 22% with the CNIT signature at 3 and at ~12 months post-KT, respectively, while the overlap was

Background. In 1872, Hartung was the first to describe the case of a fully formed mammary gland arising in the left labium majora of a 30-year-old woman. Since Hartung's initial report, 38 additional cases of ectopic vulvar breast tissue have been described. This case report describes the rare occurrence of primary mammary adenocarcinoma arising within the vulva. Case. A 64-year-old G4P4 white female presented with a 4-year history of a 2 × 1 cm firm, indurated, raised lesion of the left lateral mons. A wide local excision with ipsilateral inguinofemoral lymphadenectomy was performed. Given histological findings characteristic of both invasive ductal carcinoma and invasive lobular carcinoma, in conjunction with the presence of estrogen and progesterone receptors within the tumor, a diagnosis of infiltrating adenocarcinoma arising within ectopic breast tissue was made. Conclusions. Thirty-nine reported cases of ectopic breast tissue arising within the vulva have been reported in the world literature. Though the diagnosis of primary breast carcinoma arising within the vulva is based primarily upon histologic pattern, estrogen and progesterone receptor positivity provide supporting evidence. Given the rarity of this condition, guidelines for therapy are unavailable; we therefore suggest looking to the current management of breast cancer in order to establish a sensible approach.

Sjögren syndrome is a systemic autoimmune disease that involves the kidney as well as other organs. Tubulointerstitial nephritis secondary to monocyte, lymphocyte, and plasma cell infiltration is the characteristic lesion. The authors report a case of Sjögren related acute interstitial nephritis (AIN) with prominent neutrophilic infiltration in the interstitium. This is the first case describing predominance of neutrophilic infiltration in AIN associated with Sjögren syndrome.

Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

International audience; The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

This study compares the use of immunohistochemistry (IHC) for diagnosing carcinoma in private practice and commercial settings with use in a single academic center. HE the former group used IHC stains in 11% and the latter in 26% of cases (P < .0001). Pathologists from commercial laboratories (12% of referrals) used IHC in 38% of cases, whereas private/hospital-based community laboratories (86% of referrals) used them in 24%. The average number of stains ordered per case was similar among all groups. We suggest that the use of IHC may reflect both the degree of experience of the pathologist and the pathology practice setting. For more than 25 years, immunohistochemistry (IHC) has greatly assisted surgical pathologists in the diagnosis of neoplastic diseases. Currently, IHC has a wide variety of uses, including, but not limited to, confirmation of diagnosis, determination of the primary site of origin for metastatic tumors, classification of neoplasms, use as a prognostic and predictive biomarker, and identification of infectious organisms.

Fine-needle aspiration (FNA) is used for the diagnosis and triaging of thyroid lesions. Recently, it has been shown that the pathologic interpretation of selected thyroid specimens can show a high degree of interobserver variability (IV). Because Hurthle cells may be seen in neoplastic and nonneoplastic disease, we investigated whether pathologists consistently interpret FNA specimens from these lesions. In the present study, 22 FNA specimens that showed Hurthle cells as the predominant cell type were reviewed by 7 pathologists. Cytologic features were assessed semiquantitatively. IV was calculated, and individual case diagnoses were compared with cytologic features. IV was high before diagnoses were collapsed into like diagnoses and triage recommendations (k = 0.17, 0.44, and 0.51, respectively). Overall cellularity, number of Hurthle cells, and number of lymphocytes all correlated with collapsed diagnostic agreement, and the number of air-dried rapid Romanowsky-stained slides, overall cellularity, number of Hurthle cells, and number of lymphocytes all correlated with collapsed triage recommendations.

This chapter discusses the role of cytokeratin immunohistochemistry in the differential diagnosis of ovarian tumor. The immunohistochemical stains used to help determine the primary or secondary nature of ovarian tumors, cytokeratin differential staining, particularly cytokeratins 7 (CK7), and 20 (CK20), are among the most useful. Cytokeratins are a group of polypeptides, constituting the 7-11 nm intermediate filaments of the cytoskeleton of epithelial cells. Although 30 proteins are identified, 20 keratins, the so-called epithelial or soft keratins are the best characterized. The cytokeratins singly or in a cocktail, containing those characteristically expressed in both simple and complex epithelia, can be among the most useful antibodies. Cytokeratins 5/6 are a limited tool in the separation of ovarian involvement, by malignant mesothelioma, from papillary surface-epithelial neoplasms, in those cases, where ovarian involvement predominates and the tumor lacks the typical tubular and low-grade papillary features of most mesotheliomas. The major pitfalls in the use of cytokeratin immunohistochemical staining are also described in the chapter.

467 Background: Over the past decade, genitourinary pathologists have increasingly recognized an oncocytic variant of papillary renal cell carcinoma (PRC) that can complicate classification as Type 1 or Type 2 PRC. The International Society of Urological Pathology recently proposed reclassifying oncocytic papillary renal cell carcinoma (OPRC) as a separate subtype. We set out to test the validity of separating oncocytic tumors from other PRC. Methods: 70 consecutive cases of PRC with sufficient tissue for analysis were reviewed from patients undergoing surgery at The University of Virginia (1992 to 2007). All cases were classified by type, including those with oncocytic features. Histologic, clinical, and outcomes data were analyzed based on type and the presence of oncocytic features. Results: A total of 15 (21.4%) tumors displayed oncocytic differentiation, the majority of which were Type 2 tumors (11 or 73.3%) (p < 0.001). The male to female ratio of OPRC cases was nearly 1:1 in contrast to a significant male bias historically seen in PRC. The presence of oncocytic features was significantly associated with higher Fuhrman grade (p < 0.001) and no OPRC tumors were multifocal as opposed to 13 (23.6%) of non-OPRC tumors. At a median follow-up of 79.9 months for the entire cohort, 5-yr disease specific survival (DSS) for OPRC patients was 79.0% which was intermediate between patients with Type 1 (93.4%) and Type 2 (44.4%) tumors. By Cox proportional hazards regression analysis, DSS of OPRC patients was significantly better than Type 2 patients (HR 0.12; 95% CI 0.03, 0.52, p = 0.004), but tended to be worse than Type 1 patients (HR 2.58; 95% CI 0.78, 8.50, p = 0.12). Conclusions: We report the largest cohort of OPRC patients to date. Patients with OPRC demonstrate a survival rate intermediate between that of patients with non-oncocytic Type 1 and Type 2 PRC. Though the majority of OPRC tumors were classified as Type 2 PRC, oncocytic features complicate histomorphologic typing. Therefore, classification of OPRC separately would clarify typing of PRC and improve the validity of Fuhrman nuclear grading for PRC. Our results support separation of OPRC from Type 1 and Type 2 PRC, based on both histomorphologic typing and patient survival.

During renal ischemia-reperfusion, local and distant tissue injury is caused by an influx of neutrophils into the affected tissues. Here we measured the kinetics of margination and transmigration of neutrophils in vivo in the kidney and lungs following renal ischemia-reperfusion. After bilateral renal injury, kidney neutrophil content increased threefold at 24 h. The neutrophils were found primarily in the interstitium and to a lesser degree marginated to the vascular endothelium. These interstitial neutrophils had significantly lower levels of intracellular IFN-gamma, IL-4, IL-6, and IL-10 a tendency for decreased amounts of IL-4 and TNF-alpha compared to the marginated neutrophils. Localization of the neutrophils to the kidney interstitium was confirmed by high resolution microscopy and these sites of transmigration were directly associated with areas of increased vascular permeability. Activation of the adenosine 2A receptor significantly decreased both kidney neutrophil transmigration by about half and vascular permeability by about a third. After unilateral renal ischemia-reperfusion, the unclipped kidney and lungs did not accumulate interstitial neutrophils or have increased vascular permeability despite a marked increase of neutrophil margination in the lungs. Our findings suggest there is a sequential recruitment and transmigration of neutrophils from the vasculature into the kidney interstitium at the site of tissue injury following renal ischemia-reperfusion.