Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C‐kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106819/1/j.1365-2559.2011.03753.x.pd

Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4

Abstract Introduction Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-γ and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-γ and IL-4. Methods DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-γ and/or IL-4. Systemic IL-17, IFN-γ, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis. Results Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-γ. Neutralization of IFN-γ accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-γ/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-γ and was associated with increased bone and cartilage damage without an increase in the levels of IL-17. Conclusions IL-4 and IFN-γ both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation.http://deepblue.lib.umich.edu/bitstream/2027.42/112787/1/13075_2009_Article_2675.pd

Clear Cell Renal Cell Carcinoma With a Poorly-Differentiated Component: A Novel Variant Causing Potential Diagnostic Difficulty

Background: Several variant histologic patterns of clear cell renal cell carcinoma (RCC) are well known, especially those with sarcomatoid and rhabdoid features. However, we have encountered rare cases in which a high-grade adenocarcinoma or urothelial carcinoma-like component would be difficult to appreciate as clear cell RCC. DesignWe retrieved 26 tumors with histologically typical clear cell RCC juxtaposed to a high-grade non-clear cell component.High grade non-clear cell component was defined as non-sarcomatoid, non-rhabdoid areas that would be difficult to assign as renal cell in origin if viewed in isolation. Tumors were studied with immunohistochemistry and fluorescence in situ hybridization (FISH) or sequencing.ResultsMedian percentage of poorly differentiated component: 50%(IQR20-70). All tumors showed abrupt transition from clear cell carcinoma to poorly-differentiated (non-sarcomatoid/non-rhabdoid) areas, which showed micropapillary (7/26; 27%), urothelial-like (10/26; 39%), and adenocarcinoma NOS features (9/26; 35%). 19 tumors had necrosis. Carbonic anhydrase IX (CA-IX) was uniformly positive in well-differentiated component (20/20); poorly differentiated component showed a median positivity of 82.5% (IQR 65-100). Poorly differentiated component was positive for CK7 (5/19; 26%), CK20 (3/12; 25%), AMACR (7/12; 58%), PAX8 (12/15; 80%), and showed intact FH (6/6; 100%). CDX2 was uniformly negative. Chromosome 3p loss or VHL mutation was present in 8/13 (62%), tested with either FISH (n = 9) or sequencing (n = 4). All tested cases were negative for TFE3 (0/11) and TFEB (0/9) rearrangements on FISH. 5/21 (24%) patients were alive with metastatic disease and 5/21 (24%) had died of disease on follow up. One metastasis was composed only of the poorly-differentiated component and was near-negative for CA-IX. Conclusion: Clear cell RCC with a poorly differentiated component resembling adenocarcinoma or urothelial carcinoma is a novel source of morphologic heterogeneity that has not been previously well characterized. Potential pitfalls include decreased or absent CA-IX staining the high-grade component and aberrant positivity for cytokeratin 7 or 20. With the increasing use of renal mass biopsy and biopsies of metastatic sites for targeted therapy, pathologists should be aware of this entity and consider the possibility of clear cell RCC even for morphologically unusual tumors.https://scholarlycommons.henryford.com/merf2019caserpt/1069/thumbnail.jp

Nephrogenic Adenoma Intermixed With Urothelial Carcinoma

CONTEXT.—Nephrogenic adenoma (NA) is a common urinary tract lesion typically associated with urothelial disruption, leading to implantation of shed renal tubular cells. NA may demonstrate a spectrum of architectural and cytologic features mimicking urothelial carcinoma (UC), adenocarcinoma (including clear cell adenocarcinoma and prostatic adenocarcinoma), and invasion. However, admixed UC and NA has not been described. OBJECTIVE.—To describe cases where the NA was intimately intermixed with UC, potentially mimicking variant differentiation or invasion. DESIGN.—In 3 health care systems we identified specimens of NA and UC intimately intermixed with each other where they could mimic a spectrum of one lesion. We assessed patterns of NA and clinical implications of misdiagnosing NA as glandular differentiation of UC. RESULTS.—There were 4 women and 29 men (median age, 72 years; range, 31-89 years). Twenty-four patients had transurethral resections, 3 had biopsies, and 6 had major resections. Fourteen had noninvasive high-grade papillary UC, 6 had carcinoma in situ, and 11 had invasive high-grade UC, and in 2 patients, NA developed in a papillary urothelial neoplasm with extensive denudation. Three patients had fibromyxoid NA infiltrated by invasive UC. Classical NA (n = 30) had tubulopapillary (n = 18), pure tubular (n = 7), or pure papillary architecture (n = 5). In 1 lesion, NA was present in muscularis propria, and 2 involved adventitia. NA could have been misdiagnosed as invasion in 17 of 22 (77%) noninvasive tumors, or higher stage in 19 of 33 (58%). CONCLUSIONS.—NA can be intermingled with high-grade UC, expanding the spectrum of entities that must be considered in the differential diagnosis, as it may mimic glandular or tubular differentiation, invasion, and a higher stage of disease. Misinterpretation of NA in such a setting may incorrectly convey a more aggressive biological potential of cancer to clinicians

Renal cell tumors with an entrapped papillary component: a collision with predilection for oncocytic tumors

Renal cell tumors with mixed morphology resembling multiple renal cell carcinoma (RCC) subtypes are generally regarded as unclassified RCC. However, occasionally, papillary adenoma or RCC appears admixed with a larger, different tumor histology. We retrieved 17 renal tumors containing a papillary adenoma or papillary RCC component admixed with another tumor histology and studied them with immunohistochemistry and fluorescence in situ hybridization (FISH). Larger tumors were oncocytomas (n = 10), chromophobe RCCs (n = 5), borderline oncocytic tumor (n = 1), and clear cell RCC (n = 1). The size of papillary component ranged from 1 to 34 mm. One tumor was an oncocytoma encircled by a cyst (2.0 cm) with papillary hyperplasia of the lining. The papillary lesions were diffusely cytokeratin 7 positive (17/17), in contrast to host tumors. Alpha-methylacyl-coA-racemase labeling was usually stronger in the papillary lesions (13/15). KIT was negative in all papillary lesions and the clear cell RCC and positive in 16/16 oncocytic or chromophobe tumors. Eight of 15 (53%) collision tumors had differing FISH results in the two components. A papillary renal cell proliferation within another tumor is an uncommon phenomenon with predilection for oncocytoma and chromophobe RCC, possibly related to their common entrapment of benign tubules. When supported by distinct morphology and immunohistochemistry in these two components, this phenomenon should be diagnosed as a collision of two processes. A diagnosis of unclassified RCC should be avoided, due to potential misrepresentation as an aggressive renal cancer

#InSituPathologists: how the #USCAP2015 meeting went viral on Twitter and founded the social media movement for the United States and Canadian Academy of Pathology

Professional medical conferences over the past five years have seen an enormous increase in the use of Twitter in real-time, also known as live-tweeting . At the United States and Canadian Academy of Pathology (USCAP) 2015 annual meeting, 24 attendees (the authors) volunteered to participate in a live-tweet group, the #InSituPathologists. This group, along with other attendees, kept the world updated via Twitter about the happenings at the annual meeting. There were 6,524 #USCAP2015 tweets made by 662 individual Twitter users; these generated 5,869,323 unique impressions (potential tweet-views) over a 13-day time span encompassing the dates of the annual meeting. Herein we document the successful implementation of the first official USCAP annual meeting live-tweet group, including the pros/cons of live-tweeting and other experiences of the original #InSituPathologists group members. No prior peer-reviewed publications to our knowledge have described in depth the use of an organized group to live-tweet a pathology meeting. We believe our group to be the first of its kind in the field of pathology