Amy B.W. Chan

Hamartoma of the breast: a clinicopathological review

Aims: To review 25 cases of breast hamartoma and discuss the pathological criteria, and the usefulness of imaging modalities, fine needle aspiration cytology (FNAC), and needle core biopsy in the diagnosis. Methods: The hamartomas were assessed for interlobular fibrotic stroma, stromal adipose tissue content, pseudo-angiomatous stromal hyperplasia, and epithelial changes (hyperplasia, adenosis or apocrine metaplasia, and cyst formation). All imagings, previous FNACs, and biopsies were also reviewed. Results: Imaging (mammography, ultrasound, and magnetic resonance imaging) was performed in 18 cases, and mostly showed encapsulated masses with a heterogeneous appearance. Microscopically, all hamartomas demonstrated good demarcation with fibrous tissue condensation. Adipose tissue was noted in all cases (5–90%; mean, 31%), and interlobular fibrosis in 21 cases. Benign epithelial hyperplasia occurred in 10 cases, and pseudo-angiomatous stromal hyperplasia or cystic ducts in eight cases each. Apocrine metaplasia, calcification, stromal giant cells, and adenosis occurred in four cases or less. Two cases showed coexisting ductal carcinoma in situ limited to within the hamartoma. Needle core biopsies (four cases) and FNAC (14 cases) were largely insufficient, inconclusive, or non-specific. Conclusions: Hamartomas do not possess specific diagnostic histological features. The role of FNAC and needle core biopsy in making the diagnosis is limited, and requires clinical and radiological correlation to avoid underdiagnosis.

Strong Immunohistochemical Expression of Vascular Endothelial Growth Factor Predicts Overall Survival in Head and Neck Squamous Cell Carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality, and its relationship with tumor angiogenesis as measured by mircovessel density (MVD) or vascular endothelial growth factor (VEGF) expression has shown mixed results, with some, but not others, reporting correlation with outcome.MethodsA retrospective study of 186 patients with HNSCC was performed. Patients were evaluated for MVD and VEGF and to correlate the levels with clinical parameters, including age at diagnosis, sex, site of tumor, stage, survival (disease free and overall), pathological tumor grade, and the presence of lymph node metastases.ResultsThe 186 cancers included the following sites: oral tongue (n = 69), palate (n = 9), maxillary sinus (n = 8), floor of mouth (n = 13), oropharynx (n = 27), hypopharynx (n = 26) and larynx (n = 34). Over three-quarters of patients had advanced tumor (stage III/IV) and 58.6% had lymph node metastases. MVD and VEGF were assessed in 166 and 164 cases, respectively, but these were not correlated with site and grade. The 3-year overall and disease-free survival rates were 55.4% and 53.2%, respectively. Both univariate and multivariate survival analysis showed that advanced T stage, nodal metastasis, and strong VEGF intensity were independent adverse predictors for overall and disease-free survival. In stage IV disease, strong VEGF immunoreactivity was found to be the single adverse factor affecting the overall survival and a contributory factor for disease-free survival.ConclusionsVEGF immunoreactivity is a strong predictor of adverse outcome, particularly in locoregionally advanced disease.

Tuberculosis of the Nasopharynx: A Rare Entity Revisited

Objectives Tuberculosis of the nasopharynx is uncommon. A large series of 17 cases is reported, and the clinical and pathological features are discussed.

EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma.

We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (>/=1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.

The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer

Estrogen receptor (ER) and peroxisome proliferator‐activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied.

Trophism of neural progenitor cells to embryonic stem cells: neural induction and transplantation in a mouse ischemic stroke model.

Embryonic stem cell (ESC)–derived products have emerged as a promising cell source for neuroregeneration. C17.2 neural precursor cells were noted to express genes of neurotrophins and neuroprotective factors and to be enable to enhance proliferation, neuritogenesis, and differentiation of SH‐SY5Y and SK‐N‐AS neuroblasts, suggesting their neurotrophic potential. We used C17.2 cells as neurotrophic chaperones to induce ESCs, D3, and E14TG2a into neural lineage cells. Significantly greater numbers of Sox‐2+, Musashi‐1+, and nestin+ neurospheres developed in noncontact cocultures than in cultures of ESCs without C17.2 support or with 50% conditioned medium after 8 days. Immunoreactivity of the neuronal, astrocytic and oligodendrocytic markers was evident in cultures further differentiated for 10 days. Expression of Pax‐6, Otx‐1, and Nurr‐1 genes suggested neuroectodermal precursors in products encompassing neural stem cells, dopaminergic neurons, astrocytes, and oligodendrocytes. α‐Fetoprotein, GATA‐4, Brachyury, Nkx‐2.5, and Myf‐5 genes were not detected, indicating any mesodermal and endodermal cells. However, weak expression of Oct‐4 was noted. Behavioral assessment of ischemic mice 2 weeks after transplantation revealed significant improvement in cognitive function compared with that in ischemic sham‐operated mice. Tracking bromodeoxyuridine‐labeled products demonstrated that mostly implanted cells were localized along the needle track of the injection in the brain parenchyma, whereas some migrated to the striatum, cortex, nerve fiber bundle of the corpus callosum, and hippocampus in the ipsilateral hemisphere. One episode (of 22) of teratoma development was noted. Data from this study suggest a paradigm of trophism of neural progenitor cells for induction of ESCs into neural lineage cells.

Estrogen Receptor α Induces Prosurvival Autophagy in Papillary Thyroid Cancer via Stimulating Reactive Oxygen Species and Extracellular Signal Regulated Kinases

CONTEXT The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. OBJECTIVE This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. DESIGN The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. RESULTS ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC. CONCLUSIONS ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.

Prevalence, clinicopathological characteristics, and outcome of human papillomavirus-associated oropharyngeal cancer in Southern Chinese patients

Background: Although the global incidence of human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing, there is little information on southern Chinese population available. Methods: We analyzed 207 patients which constituted 63.5% of all newly diagnosed OPSCC in Hong Kong during a 5-year period from 2005 to 2009. Results: We used E6/7 mRNA as a marker of oncogenic involvement and found 20.8% (43/207) of OPSCC and 29.0% (36/124) of tonsillar SCC was associated with HPV. HPV-16 was identified in all cases except one (HPV-18). Patients with HPV-associated OPSCCs were significantly younger than HPV-negative patients (mean age: 59.8 vs. 63.9 years, P = 0.05). Multivariate analysis showed that HPV-associated OPSCC was more likely to occur in nonsmokers (39.5% vs. 15.1%, OR: 2.89, P = 0.05), nondrinkers (52.5% vs. 25.6%, OR: 2.72, P = 0.04), originate from the palatine tonsils (83.7% vs. 53.7%, OR: 3.88, P = 0.01), present with an early primary tumor (T1/2; 79.1% vs. 47.6%, OR: 3.81, P = 0.004), and exhibit basaloid differentiation (33.3% vs. 7.3%, OR: 19.74, P = 0.006). HPV positivity was an independent predictor for better prognosis for both 5-year overall and 5-year disease-specific survivals (DSS; 63.0% vs. 29.7%, HR: 0.33, P < 0.001, and 87.8% vs. 42.6%, HR: 0.16, P < 0.001, respectively). Conclusion: The estimated age-standardized incidence of OPSCC in Hong Kong during the period 2005–2009 was 0.12/100,000/year. Impact: This study has provided the most comprehensive clinical and pathologic information to date about this newly recognized disease in southern Chinese. In view of the global trend, we should anticipate and prepare for an increase in HPV-related OPSCC in southern China. Cancer Epidemiol Biomarkers Prev; 25(1); 165–73. ©2015 AACR.

HER2 expression predicts improved survival in patients with cervical node–positive head and neck squamous cell carcinoma

OBJECTIVE: To investigate the prognostic value of HER2 and p63 expression in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A case review of 186 HNSCCs from the oral tongue, palate, maxillary sinus, floor of mouth, oropharynx, hypopharynx, and larynx. SUBJECTS AND METHODS: All primary tumor specimens were evaluated by immunohistochemistry for HER2 and p63 expressions, which were correlated with clinical parameters including age, sex, grade, lymph node metastases, stage, and survival. RESULTS: One hundred forty-one patients had stage III-IV disease and 109 had lymph node metastases. For all cases, T and N stages were significant prognostic predictors for both overall and disease-free survivals. In the node-positive subgroup, T stage and HER2 expression were significant prognostic predictors for both overall and disease-free survivals. CONCLUSION: HER2 may be associated with longer survival in node-positive patients with HNSCC.

Inhibition of Foxp3 in cancer cells induces apoptosis of thyroid cancer cells

Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.