An Evaluation of Clinicopathological Correlation and Outcome of Human Epidermal Growth Factor Receptor 2 Subgroups Reclassified According to the Latest ASCO/CAP Guideline.

BACKGROUND: The latest American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline has updated the interpretation of uncommon human epidermal growth factor receptor 2 (HER2) in situ hybridization (ISH) patterns (groups 2-4) with concomitant HER2 immunohistochemistry, leading to changes in the diagnosis of these subgroups. We sought to assess the clinicopathological features and outcomes in these subgroups in detail with our local cohort. PATIENTS AND METHODS: Clinicopathologic features of groups 2 to 4 were compared to the typical amplified group (group 1: HER2/CEP17 ≥ 2, HER2 ≥ 4) and non-amplified group (group 5: HER2/CEP17 < 2, HER2 < 4). RESULTS: Group 2 (HER2/CEP17 ≥ 2, HER2 < 4) cases showed lower Ki67 expression and grade (P ≤ .002) than group 1 but no differences compared with group 5. Group 4 (HER2/CEP17 < 2, HER2 = 4-6) cases were associated with less necrosis, more estrogen receptor positivity, lower grade, more nodal metastases, and more special histotypes (P ≤ .037) than group 1, but higher grade and more nodal metastases (P ≤ .021) than group 5. Except for presenting as a larger tumor and of special histotypes, group 3 (HER2/CEP17 < 2, HER2 ≥ 6) cases showed no other significant differences from group 1, but were of higher grade and Ki67 level than groups 2, 4, and 5. Group 4, similar to group 5, showed worse survival than group 1 (disease-free survival: log-rank = 5.547, P = .019; overall survival: log-rank = 4.678, P = .031). The rate of relapse was similar in group 4 with and without anti-HER2 therapy, albeit with limited cases. CONCLUSION: Our findings indicate more similarities among groups 2, 4, and 5 than between groups 1 and 3, supporting the HER2 categorization in the latest guideline. Additional studies may be warranted to assess the outcomes of these patients with different management approaches.

Increased alpha-B-crystallin expression in mammary metaplastic carcinomas.

AIMS: Mammary metaplastic carcinoma is a rare breast carcinoma, and may present diagnostic difficulty. Alpha-B-crystallin has been recently reported to be expressed in basal-like and metaplastic carcinomas. METHODS AND RESULTS: Thirty-three metaplastic carcinomas, 44 conventional high-grade carcinomas and 28 mesenchymal spindle cell neoplasms as controls were assessed for their expression of αB-crystallin and conventional basal-like phenotypic markers CK5/6, CK14, p63, c-kit and epidermal growth factor receptor (EGFR) by immunohistochemistry. Alpha-B-crystallin staining was positive in 68% of the metaplastic carcinomas with cytoplasmic staining in all tumour cell components. CK5/6, CK14, p63, c-kit and EGFR stained 43%, 68%, 45%, 21% and 25% of the metaplastic carcinomas, respectively. Combining these markers, 84% of the metaplastic carcinomas expressed either αB-crystallin or CK14. In comparison, only 14% (six cases) of conventional high-grade carcinoma and 7% (two cases) of mesenchymal spindle cell neoplasm expressed αB-crystallin; all but one of these carcinomas were ER/PR/HER2 triple-negative. CONCLUSIONS: Using αB-crystallin for diagnosis of metaplastic carcinoma gives a 68% sensitivity, 88% specificity, 74% positive predictive value, 85% negative predictive value and 78% accuracy. The sensitivity is enhanced to 84% with combinations of αB-crystallin/CK14. Alpha-B-crystallin may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

Distribution of human papillomavirus genotypes among cervical intraepithelial neoplasia and invasive cancers in Macao.

Macao is a densely populated city situated in East Asia where a relatively high prevalence of human papillomavirus (HPV) types 52 and 58 has been reported in women with invasive cervical cancer. To provide data for a population-specific estimation on the impact of HPV vaccines, paraffin-embedded tissues collected from women with invasive cervical cancer or cervical intrapeitheilal neoplasia grade 2 or 3 confirmed histologically were examined for HPV using the INNO-LiPa kit. Of the 35 HPV-positive patients with invasive cancer, one HPV type was detected in 68.6%, and 31.4% were co-infected with more than one HPV type. Overall, HPV 16, HPV 18, HPV 52, and HPV 54 were the most common types found respectively in 57.1%, 17%, 11.4%, and 8.5% of patients with invasive cervical cancer. Among the 59 HPV-positive patients with cervical intraepithelial neoplasia grade 2/3, 55.9% hardbored one HPV type, and 44.1% had co-infections. The common HPV types found included HPV 16 (52.5%), HPV 52 (23.7%), HPV 58 (18.7%), and HPV 33 (17%). Although HPV 11 (a low-risk type) was also found commonly in invasive cervical cancers (14.3%) and cervical intraepithelial neoplasia grade 2/3 (15.3%), the fact that they all existed as co-infections with another high-risk type suggested HPV 11 was not the cause of the lesion. The current vaccines targeting HPV 16/18 are expected to cover 62.9-74.3% of invasive cervical cancers and 32.2-55.9% of cervical intraepithelial neoplasia 2/3 in Macao. Widespread HPV vaccination is expected to reduce substantially the disease burden associated with cervical neoplasia in Macao.

Periampullary Metastases from Breast Cancer: A Case Report and Literature Review.

We presented a metastatic breast cancer case who was afflicted with obstructive jaundice caused by an ampullary neoplasm. Since jaundice due to periampullary metastasis from breast cancer was a rare entity, a literature review of similar cases through the PubMed database was done. A total of 23 additional cases were found. Among these 24 cases, 5 presented with periampullary metastasis synchronously with the diagnosis of breast cancer, while 19 had metachronous periampullary metastasis with an interval ranging between 1.3 and 23 years from the initial diagnosis of breast cancer to the emergence of jaundice. It is intriguing to establish a differential diagnosis for common bile tract stricture prior to tissue biopsy, even with diagnostic workups including serum tumor markers, MRI plus MRCP, ERCP with intraductal brushing, and endoscopic ultrasound, in that the clinical, radiological, and endoscopic findings of metastatic lesions overlapped extensively with those found with primary periampullary malignancies. An immunohistochemical portfolio including cytokeratin7/20 (CK7/20), homeobox protein CDX2, human epidermal growth factor receptor 2 (HER2/neu), estrogen receptor alfa (ERα), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15), and transacting T-cell-specific transcription factor (GATA-3) was helpful for differential diagnosis among cases with ambiguous microscopic features.

Atypical aspirates of the breast: a dilemma in current cytology practice.

AIMS: The probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates. METHODS: A comprehensive panel of cytological features (including quantitative, cytomorphological and background features) in a large cohort of C3 breast aspirates with subsequent histological excisions was evaluated to identify relevant morphological criteria predicting the risk of subsequent malignancy. RESULTS: A total of 229 C3 specimens with histological follow-up were included. Malignant outcome was found in 30.1% of specimens and the majority were invasive cancers. Features that showed a significant association with malignant outcome included older age (p=0.001), lower percentage of epithelial cell clusters and high percentage of single cells (p=0.002), cribriform architecture in cell clusters (p=0.034), presence of intracellular mucin (p=0.027), increased cell clusters without myoepithelial cells (p=0.048), diminished fibromyxoid stromal fragments (p=0.001), reduced bipolar nuclei (p=0.021) and the presence of necrosis (p=0.023). Except for the percentages of single cells and cell clusters without myoepithelial cells, all other features were shown to be independent risk predictors in multivariate analysis. CONCLUSIONS: C3 aspirates were associated with a significant probability of histological malignancy. Certain quantitative, cytomorphological and background features were potentially helpful in predicting the risk of a malignant outcome. The prediction could be clinically useful in the management of C3 cases.

Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China.

Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients' clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia.