Fine-needle aspiration detects primary neuroendocrine carcinoma of the breast in a patient with breast implants.

Breast augmentation with implantation represents a challenge for subsequent radiographic imaging and pathological sampling. Fine-needle aspiration biopsy (FNAB) is an excellent technique to sample suspicious lesions that are adjacent to fragile implants. We report a case of a 51-year-old woman with breast implants presenting with an initial diagnosis of fibroadenoma by imaging studies. A definite diagnosis of mammary carcinoma with plasmacytoid cells was made on ultrasound (US)-guided FNAB of the breast mass with rapid on-site evaluation which initiated core needle biopsy of the mass and subsequent mastectomy with sentinel lymph node biopsy. Our case exemplifies the role of US-guided FNAB for the initial investigation of breast masses in patients with implants. In addition, the case illustrates the cytomorphological features of the tumor cells in primary neuroendocrine carcinoma of the breast.

Uterine adenosarcomas: a dual-institution update on staging, prognosis and survival.

OBJECTIVE: Uterine adenosarcomas (AS) are rare tumors thought to have a favorable prognosis. The aim of this study was to evaluate clinicopathological characteristics and treatment outcome in women with uterine AS. METHODS: Patients with uterine AS were identified from the institutional databases at two regional cancer centers, Princess Margaret Hospital, Toronto and Vancouver General Hospital. All cases underwent specialist pathological review and were re-staged according to FIGO criteria (2009). Patient demographics, treatment data and outcomes were evaluated. RESULTS: Between 1984 and 2010, 64 patients with confirmed AS were identified: 30 exhibited sarcomatous overgrowth (AS+SO). 47 patients presented with stage I disease: 27 IA and 18 IB. 57 of the 58 patients with known surgical management underwent hysterectomy: 55 having bilateral salpingo-oophorectomy, 12 having lymph node dissection. 14 patients received adjuvant treatment: 10 radiotherapy, 3 chemotherapy and 1 both. Sixteen of the 45 patients (35.6%) with follow-up recurred; median time to recurrence 21.2 months, range 2.1-87.8 months. Recurrence was associated with myometrial invasion (p=0.05). Two of the 10 women (20%) with AS+SO receiving adjuvant treatment recurred compared to 9 of the 14 (64%) who did not. One of the 5 women (20%) with stage IB disease who received adjuvant treatment recurred (20%) compared to 6 of the 7 (85.6%) who did not. CONCLUSIONS: Long term surveillance is required given the variable time to recurrence. For those with AS+SO and myometrial invasion adjuvant treatment should be considered and further investigation of adjuvant strategies is warranted.

Nested stromal epithelial tumor of the liver in Beckwith-Wiedemann syndrome.

ABSTRACT Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, congenital malformation, and tumor predisposition. Children with BWS have a higher incidence of tumors, commonly intra-abdominal tumors such as Wilms tumor, hepatoblastoma, and adrenal cortical carcinoma. Here, we describe the first case of a rare hepatic malignancy of nested stromal epithelial tumor (NSET) of the liver in a child with BWS. A 22-month old girl with BWS had a new incidental liver mass. Her alpha-fetoprotein levels were normal. She underwent a liver segmentectomy. Histopathologic features combined with immunohistochemistry results (positivity for pankeratin [AE1/3], CD56, CK19, CD117, CD99 [weak membranous pattern], ß-catenin, and WT1-COOH [focal]), were diagnostic of NSET of the liver. This is the first case of NSET of the liver associated with BWS. Its occurrence at such an early age is consistent with the tumor predisposition of BWS.

'Genetic heterogeneity' in HER2/neu testing by fluorescence in situ hybridization: a study of 2,522 cases.

Amplification for the ERBB2 oncogene encoding the HER2/neu protein (HER2) is of predictive and prognostic importance in breast carcinoma. Fluorescence in situ hybridization (FISH) is a widely accepted method for determining HER2 amplification status. A HER2-amplified tumor is defined as having a ratio of HER2 signals to chromosome 17 centromeric probe signals (HER2/CEP17 ratio) exceeding 2.2. However, the presence of scattered cells demonstrating HER2 amplification is of unclear significance. A 2009 panel guideline defined a tumor with 'genetic heterogeneity' as having at least 5% but fewer than 50% of (non-clustered) tumor nuclei with a ratio >2.2. The study objective was to examine the statistical distribution of breast tumors tested by FISH for HER2 amplification, after implementation of this 2009 guideline. We identified 2522 consecutive breast carcinoma cases (2009-2011) tested for HER2 amplification. All cases were tested by FISH using a standard clinical protocol, adhering to established guidelines. For each case, data on cell counts were retrieved electronically. Each tumor was compared with a theoretical normal distribution by quantile-quantile analysis. Of 2522 FISH tests for HER2, 1900 (75%) were non-amplified, 394 (16%) were amplified, and 228 (9%) were HER2-equivocal. A total of 666 (26%) had 'genetic heterogeneity.' Among these 'genetically heterogeneous' cases, the ratio was non-amplified in 430 (64.5%), amplified in 24 (4%), and equivocal in 212 (31.5%). The amplified subpopulation in 'genetically heterogeneous' tumors was larger if the overall ratio was close to 2.2. However, the percentage of nuclei >2.2 in a 'genetically heterogeneous' tumor was not informative of the underlying tumor-cell distribution. We conclude that the proportion of HER2-amplified nuclei within a tumor does not contribute information independent of the actual HER2/CEP17 ratio. Reassessment of the definition of 'genetic heterogeneity' in HER2 testing is warranted.

Glomus tumor presenting as a periurethral mass.

OBJECTIVES: Glomus tumors, a neoplasm arising from the glomus body, usually occur in the extremities with a particular predisposition to a subungual site. Glomus tumors are exceedingly rare in the external genitalia. In this case, the origin of a periurethral mass proved to be a glomus tumor. MATERIALS AND METHODS: A 61-year-old woman presented with postmenopausal vaginal bleeding. Clinical examination revealed a focally ulcerating, soft periurethral mass. A subsequent wedge biopsy of a periurethral, submucosal tumor was examined microscopically using both hematoxylin and eosin stains and an extensive immunohistochemical panel. RESULTS: The initial histopathologic differential diagnosis of the wedge biopsy included several neoplasms, but final analysis, including immunohistochemistry (vimentin, desmin, and calponin positivity), concluded that the lesion was a glomus tumor. CONCLUSIONS: Periurethral masses are rare and may be caused by a large number of neoplastic and nonneoplastic lesions. This case of glomus tumor presenting as a periurethral mass may be the only third reported occurrence.

Development of cell-based tuberculosis vaccines: genetically modified dendritic cell vaccine is a much more potent activator of CD4 and CD8 T cells than peptide- or protein-loaded counterparts.

Genetically modified dendritic cell (DC)-based vaccines have not been explored for immunization against tuberculosis. A gene-modified DC vaccine expressing Mycobacterium tuberculosis (M.tb) antigen 85A (Ag85A) was developed by using a recombinant replication-deficient adenoviral gene transfer vector (AdAg85A). AdAg85A-transduced DC vaccine (AdAg85/DC) expressed higher levels of IL-12 and was much more immunogenic than Ag85 protein-loaded (pro/DC) or CD4/CD8 T cell peptide-loaded (pep/DC) DC vaccines. Compared to pro/DC or pep/DC, AdAg85/DC elicited a remarkably higher level of ex vivo IFN-gamma production by CD4 and CD8 T cells at weeks 2, 6, and 12 postimmunization, which was coupled with higher frequencies of antigen-specific T cells. By an in vivo CD8 or CD4 T cell cytotoxicity (CTL) assay, AdAg85/DC was shown to provoke much higher and more sustained levels of CD8 and CD4 CTL activity up to 12 weeks postimmunization. Intramuscular (im) AdAg85/DC immunization was more potent than the iv route of AdAg85/DC immunization. Such stronger immunogenicity of im AdAg85/DC vaccination was corroborated with better protection from M.tb challenge. Our results thus suggest that genetically modified DC-based TB vaccine is superior to subunit DC vaccines and has the potential for therapeutic applications.