Among thyroid papillary carcinomas (PTCs), the follicular variant is the most common and includes encapsulated forms (EFVPTCs). Noninvasive EFVPTCs have very low risk of recurrence or other adverse events and have been recently proposed to be designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features or NIFTP, thus eliminating the term carcinoma. This proposal is expected to significantly impact the risk of malignancy associated with the currently used diagnostic categories of thyroid cytology. In this study, we analyzed the fine needle aspiration biopsy (FNAB) cytology features of 96 histologically proven NIFTPs and determined how the main nuclear features of NIFTP correlate between cytological and histological samples. Blind review of FNAB cytology from NIFTP nodules yielded the diagnosis of "follicular neoplasm" (Bethesda category IV) in 56% of cases, "suspicious for malignancy" (category V) in 27%, "atypia of undetermined significance/follicular lesion of undetermined significance" (category III) in 15%, and "malignant" (category VI) in 2%. We found good correlation (κ=0.62) of nuclear features between histological and cytological specimens. NIFTP nuclear features (size, irregularities of contours, and chromatin clearing) were significantly different from those of benign nodules but not from those of invasive EFVPTC. Our data indicate that most of the NIFTP nodules yield an indeterminate cytological diagnosis in FNAB cytology and nuclear features found in cytology samples are reproducibly identified in corresponding histology samples. Because of the overlapping nuclear features with invasive EFVPTC, NIFTP cannot be reliably diagnosed preoperatively but should be listed in differential diagnosis of all indeterminate categories of thyroid cytology.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm2 and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2− subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2− subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-3192-3) contains supplementary material, which is available to authorized users.

BACKGROUND:The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colposcopy.

Introduction: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. Methods:We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.Results: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4 þ ) programmed death 1-positive (PD-1 þ ) (>5.2%) and CD8 þ PD-1 þ (6.4%) cells, CD4 þ lymphocyte activating 3-positive (LAG-3 þ ) (>2.8% ) and CD8 þ LAG-3 þ (>2.8%) cells, CD4 þ T cell immunoglobulin and mucin domain 3positive (TIM-3 þ ) (>2.5%), and CD8 þ TIM-3 þ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes.