The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1-3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.

Utility of BRAF mutation detection in fine-needle aspiration biopsy samples read as "suspicious for papillary thyroid carcinoma".

BACKGROUND: The purpose of this study was to evaluate the diagnostic utility of BRAF mutation testing on thyroid nodules "suspicious for papillary thyroid carcinoma" (PTC) cytology. METHODS: A chart review of patients with fine-needle aspiration (FNA) results "suspicious for PTC" with subsequent thyroidectomy was performed. Corresponding archived FNA slides underwent BRAF mutation testing. RESULTS: Sixty-six patients with FNA "suspicious for PTC" underwent thyroidectomy. Forty-two (63.6%) had PTC diagnosed on final histopathology, whereas 21 (31.8%) had benign findings. Thirty-five patients (83%) with histologically proven PTC underwent total thyroidectomy, whereas 7 (17%) underwent hemithyroidectomy. BRAF mutation was detected in 17 of 49 samples (34.6%) available for testing and had 45.5% sensitivity, 87.5% specificity, 88.2% positive predictive value (PPV), and 43.8% negative predictive value (NPV) for diagnosing PTC. Two of 4 patients (50%) who underwent hemithyroidectomy with subsequent completion thyroidectomy had mutated BRAF detected. CONCLUSION: BRAF testing is a useful adjunct to improve PPV for patients with "suspicious for PTC" cytology.

Renal tubular epithelial clusters in voided urine: a potential diagnostic pitfall in renal transplant patients.

INTRODUCTION: Urine cytology is often used to screen for polyomavirus in renal transplant patients. There are qualitative cytologic differences between urine from transplant and nontransplant patients, particularly the presence of epithelial cell clusters, that can pose diagnostic difficulty. MATERIALS AND METHODS: Voided urine cytology specimens from 100 renal transplant patients and 100 nontransplant patients were reviewed for cell clusters. Immunocytochemistry for renal cell carcinoma marker (RCC) and cytokeratin 7 was performed on 10 recent specimens. Clinical data was reviewed with a focus on evidence of graft dysfunction or malignancy. RESULTS: Eighteen patients (18%) in the renal transplant group and no nontransplanted patients (0%) exhibited cell clusters with characteristic morphology: 3-dimensional cohesive groups; high nucleus-to-cytoplasm ratio; round, eccentrically placed nuclei with a prominent central nucleolus; and granular or vacuolated cytoplasm. Some had significant nuclear atypia. The groups were RCC-positive in 8 of 10 cases, and cytokeratin 7-positive in 6 of 10 cases, which is consistent with renal tubular epithelial clusters (RTECs). Clinical follow-up revealed that 88% (15 of 17) of those with RTECs developed graft dysfunction in a median of 65 days, compared with 6% (4 of 64) without RTECs (sensitivity 79%, specificity 97%, positive predictive value 88%, negative predictive value 94%). No patient developed a urinary tract malignancy. CONCLUSIONS: RTECs are relatively common in urine cytology from transplant patients, but are rare in other urine specimens. Recognition is important as they can be mistaken for urothelial carcinoma or adenocarcinoma. There appears to be a strong association with later development of graft dysfunction. These cells are most likely evidence of renal tubular injury secondary to a variety of factors, including rejection.

Solid-pseudopapillary neoplasm of the pancreas: cytomorphologic findings and literature review.

BACKGROUND: Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic malignancy with an excellent prognosis. It is most commonly diagnosed in young women. This article comprehensively reviews the clinical, pathological and radiological features of this neoplasm, as well as its clinical management. METHODS: A literature review of SPN was performed of all articles published in the English language in PubMed prior to November 1, 2013. Cytomorphological features, histopathology, immunohistochemistry, patient general demographics, molecular studies, radiologic imaging and clinical management were reviewed. RESULTS: SPN displays distinct cytomorphological features on fine-needle aspiration - thin, delicate, branching vessels in a 'Chinese character' pattern lined by one to several layers of loosely cohesive neoplastic cells. Nuclear features include indented or grooved nuclei with an evenly distributed chromatin pattern and small inconspicuous nucleoli. SPN is characteristically immunoreactive for CD10, ß-catenin (in an abnormal nuclear pattern), CD99 in a perinuclear dot-like pattern, α1-antitrypsin, and progesterone receptor. Almost all SPNs harbor an activating point mutation in exon 3 of the ß-catenin gene (CTNNB1). Clinicopathological features generally do not correlate with prognosis, and most patients experience excellent long-term survival. CONCLUSIONS: SPN can mimic other neoplasms of the pancreas, which can lead to diagnostic challenges in a limited cytologic specimen. Distinct cytomorphological features can help distinguish SPNs from other pancreatic neoplasms. Complete surgical resection as well as resection of metastatic disease is preferred given a low rate of tumor recurrence and long periods of disease-free intervals.

Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.

Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.