Alex M C Yu

Increased epidermal growth factor receptor (EGFR) expression in malignant mammary phyllodes tumors.

Mammary phyllodes tumors are uncommon stromal-epithelial neoplasms, and are divided into benign, borderline malignant and frankly malignant groups on the basis of their histological features. Accumulating evidence shows that epidermal growth factor receptor (EGFR) is involved in the pathogenesis and progression of many malignancies. This study investigated 453 phyllodes tumors (296 benign, 98 borderline, 59 malignant) for EGFR expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for gene amplification. The staining was correlated to tumor margin status, degree of malignancy, stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. Cases with strong positive IHC staining were selected for FISH. The overall positive rate for EGFR was 16.2% (48/296), 30.6% (30/98) and 56% (33/59) for benign, borderline malignant and frankly malignant phyllodes tumors, respectively. FISH demonstrated egfr gene amplification in 8% of immunohistochemically positive cases. The results of this study provide strong evidence that EGFR overexpression is involved in the pathogenesis of phyllodes tumors, although gene amplification may not be the major underlying mechanism for overexpression.

Granulomatous mastitis: the histological differentials

Background The management of granulomatous mastitis depends on the causative factor, and accurate diagnosis in distinguishing between idiopathic granulomatous mastitis (IGM) and tuberculous mastitis (TBM) is indispensable. This is particularly problematic in the cases of granulomatous mastitis in which the microbiological studies are negative. In this study, in a large cohort, the histological features for IGM and TBM were compared. Methods The histopathology files from the two participating hospitals were searched for cases of granulomatous inflammation of the breast over an 8-year period. The parameters assessed included age of patient, lesional size, systemic and local symptoms, and histological findings of inflammatory cells, granulomas, necrosis, multinucleated giant cells, fibrosis and calcifications. Results 29 cases of IGM and 33 cases of TBM were included in this study. A significant difference was seen between the two groups with regard to patient age (t=2.52, p<0.05) and lesional size (t=−5.56, p<0.01). TBM occurred in a significantly younger population, and demonstrated larger lesional sizes than IGM. There was no difference between the number of cases showing mass, local and systemic symptoms. Comparing the different histological features, the TBM group showed significantly more fibrosis, eosinophils and necrosis, whereas the IGM group showed significantly more plasma cells. Taking all the cases together as one group to evaluate the relationship between the histological parameters, there was significant positive correlation between eosinophils and fibrosis (rs=0.39, p<0.01), and negative correlation between vague and well-formed granulomas (rs=−0.38, p<0.01). Conclusion TBM was more likely to occur in younger patients, with a larger clinical mass at presentation. Histologically, TBM tends to show more eosinophils and necrosis, and IGM is associated with more plasma cells. The characteristics of the granulomas and giant cells were not distinguishing features.

αB-crystallin is a useful marker for triple negative and basal breast cancers

Tsang J Y S, Lai M W H, Wong K H Y, Chan S‐K, Lam C C F, Tsang A K H, Yu A M C, Tan P‐H & Tse G M 
(2012) Histopathology 61, 378–386

Fine needle aspiration cytology of papillary lesions of the breast - how accurate is the diagnosis?

Background: Cytological diagnosis of mammary papillary lesions is difficult. Aim: To review the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities. Methods: The cytology preparations were reviewed for: (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) background single cells; and (iv) papillary fragments and their morphology. Results: The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, 6, 14 and 3 cases of papillomas, and 6, 3 and 2 cases of papillary carcinomas showed low, moderate and high cellularity, respectively. Cell balls were present in mild to moderate number in 20 papillomas and 10 papillary carcinomas. The background single cells were absent, or present in low or moderate to high numbers in 7, 10 and 6 papillomas, and 3, 3 and 5 papillary carcinomas, respectively. Papillary fragments were absent, or present in small, moderate or large quantities in 9, 4, 8 and 2 papillomas, and 6, 3, 1 and 1 papillary carcinomas, respectively. There was no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed a higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender. Conclusion: Cytological diagnosis of papillary lesions shows a significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favour papillary carcinoma.

Biopsy sampling of breast lesions: comparison of core needle- and vacuum-assisted breast biopsies

Needle biopsy is now the initial investigation of choice for the pre-operative diagnosis of breast lesions. This includes core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) with or without radiologic assistance. The performance indices of both of these biopsy techniques were evaluated. In a large cohort of patients with breast lesions including 464 cases (285 CNB and 179 VAB), with confirmed outcomes, the diagnostic accuracy was compared using parameters including quantitation of the sampling based on the total number of cores taken, cores containing breast parenchyma, and cores with lesion; and non-epithelial changes including necrosis and calcification. CNB showed a 99% PPV, 94% NPV, 96% sensitivity, and 99% specificity, whereas VAB demonstrated a 100% PPV, 100% NPV, 100% sensitivity, and 100% specificity. The correct diagnosis in CNB was proportional to the number of cores extracted, whereas accuracy of VAB was independent of the total number of cores taken. There was a positive correlation between the presence of calcification and malignancy in CNB, but not detected under VAB. CNB and VAB were equally efficient in palpable lesions, in detecting necrosis, and calcification. Large calcification was found to be associated with malignancy in both CNB and VAB. In non-palpable lesions, VAB was more effective in the detection of calcification. The diagnostic accuracy of VAB appeared to be independent of number of cores sampled, whereas CNB required a minimum of 3–4 cores to achieve high diagnostic accuracy.

Breast cancer in the elderly: A histological assessment

Aims:  To understand the correlation between the expression status of different biological markers in breast cancers in the elderly.

Increased alpha‐B‐crystallin expression in mammary metaplastic carcinomas

Chan S‐K, Lui P C W, Tan P‐H, Yamaguchi R, Moriya T, Yu A M C, Shao M‐M, Hliang T, Wong S‐I & Tse G M
(2011) Histopathology59, 247–255

Correlation of biomarkers in head and neck squamous cell carcinoma

OBJECTIVE: To evaluate the relationship of functional magnetic resonance imaging (MRI) parameters, including choline/creatine ratio (Cho/Cr) and apparent diffusion coefficient (ADC) with protein expression of 10 common tumor and prognostic markers in head and neck squamous cell carcinoma. STUDY DESIGN: Cross-sectional study. SETTING: University hospital. SUBJECTS AND METHODS: The Cho/Cr and ADC obtained from 74 patients with head and neck squamous cell carcinoma were correlated with the expression level of the 10 protein markers as determined by immunohistochemistry. RESULTS: Cho/Cr showed significant positive correlations with cyclooxygenase 2 in primary tumors (r = 0.714), and epidermal growth factor receptor in metastatic cervical lymph nodes (r = 0.522). ADC showed significant (r = −0.591) negative correlation with human epidermal growth factor receptor 2 in metastatic cervical lymph nodes. CONCLUSION: There are relationships between protein and functional MRI markers. Future research in this direction may improve our understanding of the cancer micro-environment.

Vulvar basal cell carcinoma in China: a 13-year review

OBJECTIVE We conducted a 12-year retrospective review of vulvar basal cell carcinoma (BCC) in a Chinese population. STUDY DESIGN Medical records and histopathologic reports were examined from 5 major Hospitals in Hong Kong to list all patients diagnosed with vulvar BCC. Clinical data and histologic materials were reviewed. RESULTS Sixteen vulvar BCCs were diagnosed. Most of them were pigmented. They were removed by simple excision or wide local excision. All the carcinomas were identified in the reticular dermis. The predominant histologic pattern was nodular, which may be mistaken as adenoid cystic carcinoma. CONCLUSION The high proportion of pigmented vulvar BCCs suggested that biopsy should be performed for any pigmented lesion in a Chinese patient. The BCCs are superficial and tissue-preserving treatment approach is recommended. The tumor depth estimation is difficult and intraoperative frozen section consultation may be helpful. Formal histopathologic assessment should be used to reach an objective diagnosis.

Nerve growth factor receptor (NGFR): a potential marker for specific molecular subtypes of breast cancer

Aims Nerve growth factor receptor (NGFR) is a transmembrane receptor for the neurotrophin family. It acts either as tumour suppressor or oncogene depending on cellular context. Its role in breast cancers remained conflicting, possibly due to the heterogeneity of breast cancer subtypes. Methods In this study, we have analysed NGFR expression in 602 cases of breast cancers by immunohistochemistry. Its expression was correlated with biomarker expression and different breast cancer subtypes. Results NGFR expression was found to be positively correlated with basal markers, including Ki67, Cytokeratin (CK5/6), CK14, p63, c-kit and Epidermal growth factor receptor (EGFR) , but negatively with hormonal receptors. Among different molecular subtypes, it was negatively associated with luminal A, but positively with luminal B, and basal-like breast cancer BLBC subtypes. When comparing NGFR with other basal markers in BLBC, though less sensitive, its specificity was comparable to or better than other basal markers. For luminal B cancers, NGFR showed a high specificity which was also comparable to or better than the defining markers (estrogen receptor (ER), progesterone receptor (PR), Human epidermal growth receptor 2 (HER2) and Ki-67) for the subtype. Conclusions Overall, these findings suggested that NGFR expression could be indicative for the BLBCs or luminal B subtypes. It may represent a potential adjunct marker for these two subtypes.