Fifteen years since the first recognition of clear cell papillary renal cell carcinoma, this distinct renal tumour type is now well accepted as a distinct entity in major classification schemes. It ...occurs both with and without end-stage renal disease and may be multifocal or bilateral in both scenarios. Recognisable morphological features include clear cells lining branching glands and variable papillary formations with nuclear alignment. Most tumours are small (pT1a) and nucleolar grade 1–2. Immunohistochemistry consistently shows positivity for carbonic anhydrase IX and cytokeratin 7, and often high molecular weight cytokeratin or GATA3, the latter suggesting distal nephron phenotype. Labeling for AMACR and CD10 is consistently negative or minimal. Despite a resemblance to clear cell renal cell carcinoma, molecular alterations of VHL and chromosome 3p are typically lacking, with debatable rare exceptions. Potential mimics include clear cell renal cell carcinoma (with branching architecture or nuclear alignment), papillary renal cell carcinoma with clear cytoplasm, or rarely MITF family translocation renal cell carcinoma. Clinical behaviour is highly favourable with rare, debatable reports of aggressive behaviour. Combined with striking similarity to several extrarenal benign neoplasms, it would be reasonable to reclassify this entity as a benign or low malignant potential neoplasm. Using the nomenclature of the extrarenal counterparts, clear cell papillary (cyst)adenoma is proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Renal cell carcinoma (RCC) is unusual among cancers in that it often grows as a spherical, well‐circumscribed mass. Increasing tumour size influences the pathological pT stage category within pT1 and ...pT2, with cutoffs of 40, 70 and 100 mm; however, with increasing size also comes a sharp increase in the likelihood of renal sinus or renal vein tributary invasion, such that clear cell RCC rarely reaches 70 mm without invading one of these. To clarify some previous challenges in assigning tumour stage, the American Joint Committee on Cancer 2016 tumor–node–metastasis classification has removed the requirements than vein invasion be recognised grossly and that vein walls contain muscle for the diagnosis of vein invasion. Renal pelvis invasion has also been added as an additional route to pT3a. Multinodularity or finger‐like extensions from a renal mass should be viewed with great suspicion for the possibility of vein or renal sinus invasion, and, as tumour size increases to over 40–50 mm, thorough sampling of the renal sinus interface should always be undertaken. With increasing interest in adjuvant therapy in renal cancer, the pathologist's role in RCC staging will continue to be an important prognostic parameter and a tool for selection of patients for enrolment in clinical trials.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice ...require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following(1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging–targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.
Activating mutations in EGFR predict benefit from tyrosine kinase inhibitor therapy for patients with advanced non-small cell lung cancer. Directing patients to appropriate therapy depends on ...accurate and timely EGFR assessment in the molecular pathology laboratory. This article describes the analytical design, performance characteristics, and clinical implementation of an assay for the rapid detection of EGFR L858R and exon 19 deletion mutations. A droplet digital polymerase chain reaction (ddPCR) assay was implemented with probe hydrolysis-dependent signal detection. A mutation-specific probe was used to detect EGFR L858R. A loss of signal design was used to detect EGFR exon 19 deletion mutations. Analytical sensitivity was dependent on DNA input and was as low as 0.01% variant allele fraction for the EGFR L858R assay and 0.1% variant allele fraction for the EGFR exon 19 deletion assay. Correlation of 20 clinical specimens tested by ddPCR and next generation sequencing showed 100% concordance. ddPCR showed 53% clinical sensitivity in the detection of EGFR mutations in plasma cell-free DNA from patients with lung cancer. The median clinical turnaround time was 5 days for ddPCR compared to 13 days for next generation sequencing. The findings show that ddPCR is an accurate and rapid method for detecting EGFR mutations in patients with non-small cell lung cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Staging of bladder cancer Magers, Martin J; Lopez‐Beltran, Antonio; Montironi, Rodolfo ...
Histopathology,
January 2019, Volume:
74, Issue:
1
Journal Article
Peer reviewed
Urothelial carcinoma of the urinary bladder is a heterogeneous disease with multiple possible treatment modalities and a wide spectrum of clinical outcome. Treatment decisions and prognostic ...expectations hinge on accurate and precise staging, and the recently published American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition, should be the basis for staging of urinary bladder tumours. It is unfortunate that the International Union Against Cancer (UICC) 8th edition failed to incorporate new data which is considered in the AJCC 8th edition. Thus, the AJCC 8th edition is the focus of this review. Several critical changes and clarifications are made by the AJCC 8th edition relative to the 7th edition. Although the most obvious changes in the 8th edition are in the N (i.e. perivesical lymph node involvement now classified as N1) and M (i.e. M1 is subdivided into M1a and M1b) categories, several points are clarified in the T category (e.g. substaging of pT1 should be attempted). Further optimisation, however, is required. No particular method of substaging pT1 is formally recommended. In this review, these modifications are discussed, as well as points, which require further study and optimisation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary Renal oncocytoma and chromophobe renal cell carcinoma (RCC) have been long recognized as distinct tumors; however, it remains unknown if uniform diagnostic criteria are used to distinguish ...these tumor types in practice. A survey was distributed to urologic pathologists regarding oncocytic tumors. Responses were received from 17/26 invitees. Histologically, >1 mitotic figure was regarded as most worrisome (n = 10) or incompatible (n = 6) with oncocytoma diagnosis. Interpretation of focal nuclear wrinkling, focal perinuclear clearing, and multinucleation depended on extent and did not necessarily exclude oncocytoma if minor. Staining techniques most commonly used included: CK7 (94%), KIT (71%), vimentin (65%), colloidal iron (59%), CD10 (53%), and AMACR (41%). Rare CK7-positive cells (≤5%) was regarded as most supportive of oncocytoma, although an extent excluding oncocytoma was not universal. Multiple chromosomal losses were most strongly supportive for chromophobe RCC diagnosis (65%). Less certainty was reported for chromosomal gain or a single loss. For tumors with mixed or inconclusive features, many participants use an intermediate diagnostic category (82%) that does not label the tumor as unequivocally benign or malignant, typically “oncocytic neoplasm” or “tumor” with comment. The term “hybrid tumor” was used variably in several scenarios. A slight majority (65%) report outright diagnosis of oncocytoma in needle biopsies. The morphologic, immunohistochemical, and genetic characteristics that define oncocytic renal tumors remain incompletely understood. Further studies correlating genetics, behavior, and histology are needed to define which tumors truly warrant classification as carcinomas for patient counseling and follow-up strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show ...variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69 y), and the M:F ratio was 2.2:1. Median tumor size was 6.5 cm (range, 2.5 to 28 cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118 mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9 y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.
A subset of renal cell neoplasms contains a mesenchymal stromal component, often resembling smooth muscle. To date, it remains debated whether these represent one or more distinct pathological ...entities. The foremost of these, renal cell carcinoma with angioleiomyoma-like stroma (also known as smooth muscle or leiomyomatous stroma), has some distinctive features, including immunohistochemical positivity for cytokeratin 7 and often a lack of genetic changes of clear cell renal cell carcinoma. It is debated whether this is related to the much more common clear cell papillary renal cell carcinoma, owing to the substantial similarity of their immunohistochemical phenotypes. The term renal angiomyoadenomatous tumour has been used by some authors in this context, but this is a source of controversy with some believing it is synonymous with clear cell papillary renal cell carcinoma. Smooth muscle-rich renal cancers appear to be enriched in tuberous sclerosis complex patients, but it is likely that these occur sporadically also. Recently, renal cell carcinomas with TCEB1 mutation and monosomy of chromosome 8 have also been reported. These have been noted to have fibromuscular stroma and cytokeratin 7 reactivity; however, absence of these genetic alterations in renal cell carcinomas with smooth muscle stroma suggests that this represents only one of likely several entities. Other uncommon patterns of renal neoplasms, such as clear cell renal cell carcinoma with degenerative fibrosis or haemangioma-like changes, mixed epithelial and stromal tumour with epithelial proliferation, angiomyolipoma with epithelial cysts, renal cell carcinoma with associated angiomyolipoma, and sarcomatoid renal cell carcinoma may cause diagnostic challenges for the pathologist. Although knowledge of renal cell carcinomas with a stromal component has dramatically increased recently, further study is necessary to understand the molecular pathology of these tumours and if they have implications for inherited tumour syndromes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the increasing number of newly identified renal neoplasms, the diagnosis of renal cell carcinoma (RCC) can usually be reached with careful histologic examination and a limited ...immunohistochemical (IHC) panel. Clear cell, papillary, chromophobe RCC and oncocytoma account for more than 90% of renal neoplasia in adults, and sophisticated ancillary tools are usually unnecessary. Renal tumors with entity-defining genetic alterations may ultimately require molecular confirmation via cytogenetics or sequencing technologies, such as RCC with TFE3, TFEB, or ALK gene rearrangements, or TFEB amplified RCC. In fumarate hydratase-deficient and succinate dehydrogenase-deficient RCC, highly specific IHC markers can strongly suggest the diagnosis. In the metastatic setting, PAX8 and carbonic anhydrase 9 are among the most helpful markers for confirming RCC and clear cell type, respectively; however, caution should be exercised in the absence of a current or historical renal mass. In diagnostically challenging cases, such as renal eosinophilic tumors with low-grade nuclear features, or infiltrative high-grade tumors, careful examination coupled with a judicious panel of IHC markers usually resolves the diagnosis. This review offers concise algorithms for diagnosis of kidney neoplasia with the latest recognized, provisional, and emerging entities to daily pathology practice.
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