Role of Ancillary Techniques in Fluid Cytology.

The cytologic evaluation of serous effusions may be challenging for a number of reasons. Distinction of benign, reactive conditions from malignancy represents the main focus when examining these specimens. The morphologic diagnosis of malignancy may be difficult due to the relative paucity of abnormal cells.

Molecular profiling of neuroendocrine malignancies to identify prognostic and therapeutic markers: a Fox Chase Cancer Center Pilot Study.

Background: The rarity of neuroendocrine malignancies limits the ability to develop new therapies and thus a better understanding of the underlying biology is critical.

Methods: Through a prospective, IRB-approved protocol, patients with neuroendocrine malignancies underwent next-generation sequencing of their tumours to detect somatic mutations (SMs) in 50 cancer-related genes. Clinicopathologic correlation was made among poorly differentiated neuroendocrine carcinomas (NECs/poorly differentiated histology and Ki-67 >20%) and pancreatic neuroendocrine tumours (PanNETs/Ki67 ⩽20%) and non-pancreatic neuroendocrine tumours (NP-NETs/Ki67 ⩽20%).

Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.

Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT.

Subclassification of non-small cell lung cancer by cytologic sampling: a logical approach with selective use of immunocytochemistry.

Objectives: To determine the diagnostic accuracy of cytomorphology for subclassifying non-small cell lung cancer into adenocarcinoma (AC) and squamous cell carcinoma (SqC), and the utility of immunocytochemistry (ICC) for poorly differentiated cases.

Study Design: Preoperative cytologic diagnoses of SqC, AC, or non-small cell carcinoma (NSCC) were compared with surgical resection diagnoses. NSCC cases with adequate cell block material were stained with CK7, CK5/6, TTF-1 and p63 antibodies and subclassified as SqC, AC, or equivocal.

Clinical Stage T1 micropapillary urothelial carcinoma presenting with metastasis to the pancreas.

Micropapillary carcinoma of the bladder is an extremely aggressive variant of urothelial carcinoma. Radical cystectomy is the standard treatment for all patients, including those with nonmuscle-invasive disease. We present a patient diagnosed with clinical Stage T1 micropapillary carcinoma of the bladder who was found to have a 2-cm metastasis to the head of the pancreas.

Small-cell carcinoma with an epidermal growth factor receptor mutation in a never-smoker with gefitinib-responsive adenocarcinoma of the lung.

Activating mutations in the epidermal growth factor receptor (EGFR) gene are extremely rare in small-cell lung cancer (SCLC). Here, we present a case of an EGFR-mutant gefitinib-responsive non-small-cell lung cancer (NSCLC) of adenocarcinoma histology occurring in a never-smoker followed by subsequent diagnosis of metastatic SCLC carrying an EGFR mutation. Although gefitinib therapy of the primary NSCLC resulted in disease control for over 3 years, the patient subsequently developed metastatic SCLC to the liver.

The cytologic criteria of malignancy.

Cytology and cell biology are two separate fields that share a focus on cancer. Cancer is still diagnosed based on morphology, and surprisingly little is known about the molecular basis of the defining structural features. Cytology uses the smallest possible biopsy for diagnosis by reducing morphologic "criteria of malignancy" to the smallest scale.

Quantitative methylation-specific PCR for the detection of aberrant DNA methylation in liquid-based Pap tests.

Background: Aberrant promoter methylation of selective tumor suppressor genes has been detected in squamous intraepithelial lesions (SIL) and invasive cervical cancer. Identification of methylation profiles of genes that can distinguish high-grade SIL (HSIL) from low-grade SIL (LSIL), and cytologically negative for intraepithelial lesion or malignancy (NILM) residual liquid-based Papanicolaou (Pap) tests may be potentially useful as an ancillary test for cervical cancer screening.

Methods: Using real-time quantitative methylation-specific polymerase chain reaction (PCR) (QMSP), the authors analyzed the frequency and relative level of promoter methylation for DAPK1, IGSF4, SPARC, and TFPI2 in biopsy-confirmed HSIL and LSIL, and NILM residual liquid-based Pap tests.

Locked nucleic acids can enhance the analytical performance of quantitative methylation-specific polymerase chain reaction.

Aberrant DNA methylation of tumor suppressor genes is a frequent epigenetic event that occurs early in tumor progression. Real-time quantitative methylation-specific polymerase chain reaction (QMSP) assays can provide accurate detection and quantitation of methylated alleles that may be potentially useful in diagnosis and risk assessment for cancer. Development of QMSP requires optimization to maximize analytical specificity and sensitivity for the detection of methylated alleles.

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" is a distinct cytologic category: histologic outcomes and HPV prevalence.

We examined the histologic outcomes and prevalence of high-risk human papillomavirus (HR-HPV) in women with liquid-based Papanicolaou (Pap) tests interpreted as "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) compared with the 2001 Bethesda System (TBS 2001) cytologic categories of LSIL, high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A computer search identified 426 LSIL, 86 ASC-H, 81 LSIL-H, and 110 HSIL cytologic interpretations during a 1-year period, each with up to 2 years of histologic follow-up. The risk of histologic cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 2+) associated with LSIL-H (32/81 [40%]) was intermediate between LSIL (46/426 [10.

"Sip volume" as a quality indicator in liquid-based cervical cytology.

Background: Introduction of nonmicroscopic cervical screening techniques creates the potential for liquid-based cytology specimens to be sent for human papillomavirus (HPV) testing, automated screening, or other assays prior to microscopic quality assessment. It was hypothesized that the volumes required to prepare ThinPreps ("sip volumes") represent indicators of specimen quality.

Methods: A stratified random sample of 505 enrollment ThinPreps were assessed in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) to evaluate associations between sip volume and slide cellularity, cellular distribution, and clinical outcomes.

Induction of the tumor-suppressor p16(INK4a) within regenerative epithelial crypts in ulcerative colitis.

p16(INK4a) is a major tumor-suppressor protein, but its regulation and settings of fuction remain poorly understood. To explore the notion that p16 is induced in vivo in response to replicative stress, we examined p16 expression in tissues from human ulcerative colitis (UC; n = 25) and normal controls (n = 20). p16 was expressed strongly in UC-associated neoplasms (n = 17), as seen previously in sporadic colonic neoplasms.

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma.

Purpose: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs.

Experimental Design: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004.

Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed.

Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed.

DNA methylation profiling of cervical squamous intraepithelial lesions using liquid-based cytology specimens: an approach that utilizes receiver-operating characteristic analysis.

Background: Cervical carcinoma is a common malignancy among women worldwide, and its pathogenesis is related causally to human papillomavirus infection. The progression from precursor squamous intraepithelial lesions to cervical carcinoma requires additional genetic and epigenetic alterations that have not been characterized fully. The authors examined aberrant promoter methylation of multiple tumor suppressor genes in precursor squamous intraepithelial lesions.

A GATA factor mediates cell type-restricted induction of HLA-E gene transcription by gamma interferon.

The human major histocompatibility complex (MHC) class Ib gene, HLA-E, codes for the major ligand of the inhibitory receptor NK-G-2A, which is present on most natural killer (NK) cells and some CD8(+) cytotoxic T lymphocytes. We have previously shown that gamma interferon (IFN-gamma) induction of HLA-E gene transcription is mediated through a distinct IFN-gamma-responsive element, the IFN response region (IRR), in all cell types studied. We have now identified and characterized a cell type-restricted enhancer of IFN-gamma-mediated induction of HLA-E gene transcription, designated the upstream interferon response region (UIRR), which is located immediately upstream of the IRR.

Peroxisome proliferator-activated receptor gamma expression in follicular-patterned thyroid lesions. Caveats for the use of immunohistochemical studies.

To determine its usefulness as a specific diagnostic marker for follicular carcinomas (FCs) vs other follicular-patterned thyroid lesions and possible application to fine-needle aspiration specimens, we immunohistochemically studied peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in histologic sections (FC, 13 cases; follicular adenoma [FA], 11; follicular variant of papillary carcinoma [FVPC], 9) and surrounding thyroid tissue by using a PPAR gamma monoclonal antibody. Positivity (detected by nuclear staining) was scored as absent, weak, moderate, or strong. When only moderate or strong nuclear staining was considered positive, 9 FCs (69%), 3 FAs (27%), and 2 FVPCs (22%) demonstrated positive nuclear immunoreactivity.

Retropharyngeal lipoma causing obstructive sleep apnea: case report including five-year follow-up.

Objectives/hypothesis: Lipomas of the retropharyngeal space are rare and do not cause symptoms until they reach a large size. Although retropharyngeal lipoma is an uncommon entity, several reports of it appear in the literature, and the treatment has routinely been surgical excision. Such fatty tumors also carry the rare possibility of being liposarcomas, which further warrants their excision.

Peripheral endothelial cells are not reliable in differentiating primary benign and malignant hepatocellular lesions in fine needle aspirates of the liver.

The distinction of hepatocellular carcinoma (HCC) from benign lesions of the liver in fine needle aspiration (FNA) specimens can be problematic. In an attempt to separate well-differentiated HCC from benign hepatocellular lesions, the presence of tissue fragments displaying peripheral endothelial cells (PE) has been proposed in a previous study as a useful feature in favour of malignancy. In this study, we evaluated slides from 59 cases of liver masses undergoing FNA (19 HCC, 40 benign) and evaluated them for the presence of tissue fragments containing PE.