Eric Burks

CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells.

CD4(+) CD56(+) lineage-negative malignancies are difficult to diagnose and classify. Recent studies have suggested that these malignancies may derive from plasmacytoid dendritic cells (pDC). In this report, we examine 10 cases of CD4+, CD56+ lineage-negative malignancies that presented in various tissue sites. The goal was to identify the morphologic, immunophenotypic, and genotypic findings to devise a diagnostic approach to tissue biopsies of these lesions and to confirm the proposed cell of origin. The mean age was 66 years (range, 45-80 years) with a male predominance (8 males/2 females). Frequent sites of disease included skin (60%) and peripheral blood/bone marrow (70%). Tumor cells were positive for CD45, CD43, CD4, and CD56 (9 of 10). The pDC markers, CD123 (9 of 10) and CD45RA (10 of 10), were detected by immunoperoxidase staining. Also noted was CD2 positivity (1 case), weak CD7 positivity (4 of 8 cases), weak CD33 (4 of 9 cases), TdT (2 cases), and CD68 (2 cases). All cases were otherwise negative for EBV (EBER), B-cell, T-cell, myeloid, and NK cell markers. T-cell receptor-γ gene rearrangement was negative in all cases. Complex structural chromosomal abnormalities were seen in 3 of 5 cases, a subset of which may be recurrent in pDC malignancy. Overall prognosis was poor despite multiagent chemotherapy and/or radiation. Our study confirms that CD4+/CD56+ lineage-negative tumors are derived from pDC and have characteristic clinical, histopathologic, and immunophenotypic features. Furthermore, these rare neoplasms can be readily diagnosed using recently developed immunoperoxidase techniques.

Follicular pancreatitis: a distinct form of chronic pancreatitis—an additional mimic of pancreatic neoplasms

Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, κ and λ light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers.

Is there a gain in chromosome 3q in the pathway to anal cancer

BACKGROUND: Chromosome 3q gain has been identified in human papillomavirus–infected cervical cancer cells. OBJECTIVE: We sought to identify the presence of chromosomal 3q gain in anal neoplasia. DESIGN: This was a retrospective cohort. SETTINGS: The study was conducted in a group colorectal surgery practice. PATIENTS: Fifty-two patients with no dysplasia, low-grade dysplasia, high-grade dysplasia, or anal cancer were studied. INTERVENTIONS: Pairs of biopsy specimens were paraffin embedded and reviewed. One of each slide pair was stained with hematoxylin and eosin and the second processed for fluorescence in situ hybridization. The hybridized set was deparaffinized first and then hybridized with a probe for the chromosome 3q26 region. Then, slides were scanned using an automated fluorescence microscopy system that analyzed defined areas of the tissue to enumerate all of the nuclei for hybridized probe signals to detect chromosome 3q gain. MAIN OUTCOME MEASURES: We measured for gain in chromosome 3q26. RESULTS: We identified chromosome 3q gain in 7 (78%) of 9 patients with squamous-cell cancer, 8 (53%) of 15 high-grade dysplasia samples, 0 of 12 low-grade dysplasia samples, and 0 of 16 samples with no dysplasia. The sensitivity for high-grade or invasive neoplasia was 58%, with a specificity of 100%. The positive predictive value of the test was 100% for detecting high-grade dysplasia and/or squamous-cell cancer from no dysplasia, and the negative predictive value of the test was 62%. LIMITATIONS: This study was limited by its small sample size and retrospective design. CONCLUSIONS: Chromosome 3q gain represents an important shared pathway to tumorigenesis in cervical and anal neoplasia. Multiple potential diagnostic roles exist for this easily performed test in the evaluation of anal neoplasia.

Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma

To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer‐specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue.

Does reevaluation of colorectal cancers with inadequate nodal yield lead to stage migration or the identification of metastatic lymph nodes

BACKGROUND: The National Comprehensive Cancer Network recommends routine reevaluation of all stage II colon cancer specimens with fewer than 12 lymph nodes. However, there are few data demonstrating the effect of reevaluation on stage. OBJECTIVE: The aim of this study was to demonstrate the effect of pathologic reevaluation for colorectal cancers with fewer than 12 lymph nodes on stage. DESIGN: This study entailed a retrospective review of pathology reports. SETTINGS: This study was conducted at 2 large multispecialty referral centers. INTERVENTIONS: Pathologic reevaluation was performed to look for additional lymph nodes. PATIENTS: All patients with stage I through III colorectal cancers with inadequate lymph node yields who underwent reevaluation from January 1, 2007 through March 31, 2011 were identified. MAIN OUTCOME MEASURES: We recorded initial pathologic stage and new stage following reevaluation. The following variables before and after reevaluation were also recorded: 1) total lymph node count, 2) metastatic node count, 3) negative node count, and 4) lymph node ratio. RESULTS: Eighty-three patients underwent pathologic reevaluation from a total of 1682 cancer specimens. Mean nodal yields were 7.2 ± 2.6 on the first pathologic review. On reevaluation, 80% of patients had one or more newly identified nodes. On average, 6.9 ± 9.6 more lymph nodes were identified with a metastatic node detected in 4 of 83 patients (4.8%). After pathologic reevaluation, 1 patient (1.2%) had a change in TNM stage from N1 to N2 disease. The lymph node ratio changed in 13 of 15 patients (87% of stage III cancers). Only 4 of these had a change in lymph node quartile. LIMITATIONS: The study was limited by its retrospective nature and small sample size. CONCLUSION: Few patients have a newly discovered metastatic node or stage change following pathologic reevaluation. The effect of pathologic reevaluation on treatment and outcome should be further investigated.

MicroRNA expression profiles in upper tract urothelial carcinoma differentiate tumor grade, stage and survival: implications for clinical decision-making

OBJECTIVE To evaluate microRNA (miRNA) biomarkers for upper tract urothelial carcinoma (UTUC) to improve risk stratification. METHODS miRNA was isolated from 157 radical nephroureterectomy specimens from 2 institutions. The relative expression of miRNA was examined for high grade vs low grade tumors as well as muscle invasive vs nonmuscle invasive tumors. Recurrence free survival (RFS) and overall survival (OS) were also stratified using relative expression of specific miRNA. RESULTS The optimized model to identify high grade UTUC included miR-29b-2-5p, miR-18a-5p, miR-223-3p, and miR-199a-5p, generating a sensitivity of 83%, specificity of 85%, and generated a receiver operating characteristic (ROC) curve with area-under-the-curve of 0.86. Similarly, the model classifier for predicting ≥pT2 disease incorporated miR-10b-5p, miR-26a-5p-5p, miR-31-5p, and miR-146b-5p, producing a sensitivity of 64%, specificity of 96%, and area-under-the-curve of 0.90. RFS was best reflected by a combination of miR-10a-5p, miR-30c-5p, and miR-10b-5p, while OS was best predicted by miR-10a-5p, miR-199a-5p, miR-30c-5p, and miR-10b-5p. CONCLUSION High-grade vs low-grade as well as muscle invasive vs nonmuscle invasive UTUC can be reliable distinguished with unique miRNA signatures. Furthermore, differential expression of UTUC miRNA produces robust classifiers for predicting RFS and OS that may help identify patients who would most benefit from adjuvant therapies.