Tumor-associated macrophages play a crucial role in breast cancer progression and tumor angiogenesis. However, evaluation of tumor-associated macrophages incorporating their histological locations is lacking. The aim of this study was to clarify whether macrophages in tumor stroma and macrophages in tumor cell nests have distinctive properties in relation to pertinent breast cancer clinicopathological parameters and tumor angiogenesis. In 94 human invasive breast ductal carcinomas, tumor-associated macrophages were immunostained with anti-CD68 antibody and counted or graded according to these histological locations. Microvessels were immunostained with anti-CD34 antibody and counted for microvessel density. We found that the presence of tumor stromal and tumor nest macrophages was closely correlated (p = 0.001). Both tumor stromal and tumor nest macrophages were associated with mitotic count (p = 0.001 and p = 0.037, respectively). However, only higher tumor stromal macrophage grades were associated with higher tumor grades (p = 0.004) and negative estrogen receptor status (p = 0.007). Multivariate analysis showed that tumors with a high mitotic count score (score 3 vs. scores 1 and 2) had a higher tumor stromal macrophage density (Grades III and IV) when adjusted for tumor size, tubule formation, and estrogen receptor status (odds ratio 3.41, p = 0.010). The tumor nest macrophage count significantly correlated with the microvessel density (p
This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
Penicillamine toxicity in Wilson's disease has been well reported but rarely seen now as newer agents are being used. We present a case who developed multiple rare complications of Penicillamine concurrently. Our patient is one of three siblings on Penicillamine, she was the only one who developed massive breast enlargement four months after commencing Penicillamine therapy, as well as dermatological adverse reactions and myasthenia gravis three more months later. All the adverse effects improved soon after substitution of the offending agent with Trientine.
Prebiopsy localization of impalpable breast lesions (IBL) assures removal of suspicious mammographically detected lesions. Specimen radiograph of the excised specimen is mandatory to confirm complete excision. The aim of this study was to audit our series of percutaneous hookwire localization and to determine the positive biopsy rate of the mammographically detected impalpable breast lesion in our center. Thirty-eight patients with suspicious IBL underwent excision biopsy under mammographic localization in our unit from late February 1998 to May 2003. The excised specimen is immobilized and compressed within the Transpec device. This device incorporates a reference grid visible in the specimen radiograph. Hence, the target lesion marked in the reference grid of the specimen radiograph will allow precise examination and exact localization of the suspicious lesion by the pathologist. The positive biopsy rate for malignant lesion was 26.3%, the majority fall in the range of 40-59 age group. Thirty-two (84.2%) of the patients had clustered micro-calcifications, 4 (10.5%) had impalpable mass lesions and in 2 (5.3%) spiculated lesions were seen on the preoperative mammogram. Mammographic feature of clustered micro-calcification accounts for all the malignant lesions in our series. Utilization of Transpec device has shown to be practical, reliable and cost effective in the management of IBL. Nonetheless, it should be emphasized that optimal specimen radiography and pathological correlation requires close cooperation between radiologist, surgeon and pathologist.
This is a review of the positive biopsy rate of nonpalpable breast lesions detected on mammography. The histology of 130 hookwire excision biopsy from 1990 to 1995 and the cytology of 39 stereotactic fine needle aspiration cytology in 1995 were reviewed. The yearly positive biopsy rate of each procedure was determined. In 1990, the positive biopsy rate for hookwire excision biopsy was 15%, in 1991 20%, in 1992 11%, in 1993 17%, in 1994 33% and in 1995 39%. In 1995, the positive biopsy rate for stereotactic fine needle aspiration cytology was 21%. The positive biopsy rate for hookwire excision biopsy had improved from 15% in 1990 to 39% in 1995.
Radiologically guided localization procedures are indicated pre-operatively when breast lesions are nonpalpable. The results of 42 percutaneous hookwire localizations over a period of 3 years are described. Of the total, 7 (17%) were found to be malignant. Biopsy was indicated by mammographically detected mass in 48%, by microcalcifications in 40% and by microcalcifications with an associated mass in 12%.
The breast clinic in the university Hospital Kuala Lumpur was started in August 1993 to cater for the increasing number of women seeking treatment for breast complaints. A four-month survey carried out from January to April 1994 found that Chinese women are more "breast conscious" than Malay and Indian women. The majority of patients were in the reproductive age group. Benign breast diseases form the majority of cases of breast diseases seen. The pick-up rate for new cases of breast cancer was 3.1%. Fine needle aspiration biopsy had a 100% sensitivity during the four-month study, and was a quick method of obtaining a diagnosis.
Study site: Breast clinic, University Malaya Medical Centre (UMMC)
A 26-year-old assistant nurse suffered from acute lymphoblastic leukemia and was successfully treated with combination chemotherapy. 15 months later, she relapsed with a lump in her right breast. The significance of this finding is discussed.
Chronic Granulomatous Mastitis (CGM) is a rare disorder and this generally occurs in young women with a recent history of lactation. Development of this disease in nulliparous women are rare with an incidence of 10%. Axillary lymphadenopathy is seen in 15% of cases diagnosed with CGM. We present a case of CGM in a 23- year-old nulliparous woman presenting with a breast mass and multiple axillary lymphadenopathy. To the best of our knowledge there are no documented cases of both these rare clinical features occurring simultaneously. The use of oral steroids prevented surgery and effectively induced remission.
Neuroendocrine carcinomas of the breast are uncommon tumors known to occur in the elderly. While focal neuroendocrine differentiation may be noted in many ductal and lobular carcinomas, the term neuroendocrine carcinoma is to be applied when more than 50% of the tumor shows such differentiation. This case report details the cytological features of a neuroendocrine carcinoma that was encountered in our hospital. The fine needle aspiration (FNA) smears showed discohesive polygonal cells with abundant cytoplasm, many of which contained eosinophilic granules located at one pole. Histology of the mastectomy and axillary lymph nodes specimen from this patient showed features of neuroendocrine carcinoma--solid type, with metastasis, confirmed with immunohistochemistry. The patient is disease free seven months after surgery. This case highlights the need to closely observe cytological details to identify this rare tumor that may otherwise appear to be invasive duct carcinoma--not otherwise specified on FNA. The implications of diagnosing neuroendocrine differentiation for prognosis and management are also discussed.
Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.
One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.
Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the breast in 918 cases is presented. Correlation between the FNA cytology and subsequent histology of the lesions was available in 211 cases. FNA had a sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall diagnostic accuracy rate was 95.7%.
The primary objective of this study was to determine the mean glandular dose (MGD) during diagnostic mammography in Malaysia. The secondary objective was to evaluate some of the factors affecting MGD. A survey of standard MGD was performed, based upon quality control records for the period October 1999 to August 2001. This covered 30 mammography units from 9 manufacturers. MGD was also measured for a series of patients attending mammography examinations at three other mammography units. MGD per film was estimated from recorded radiographic factors, the compressed breast thickness (CBT) and X-ray unit calibration data. MGD per woman was calculated by summing the MGDs for all films, and averaging it over both breasts. 300 women drawn equally from three major ethnic groups, namely Malay, Chinese and Indian, took part in the study. The difference of MGD per woman between ethnic groups was tested for significance using non-parametric Kruskal-Wallis and median tests. The factors affecting MGD per woman were tested for significance using a multivariate analysis of variance. The MGD for the phantom was 1.23 mGy (range 0.22-2.39 mGy) while the mean patient based MGD per film was 1.54 mGy and 1.82 mGy for the craniocaudal and mediolateral oblique views, respectively. The mean MGD per woman was 3.37 mGy. It was also found that there is no significant difference in MGD per woman among the ethnic groups (p>0.05, Kruskal-Wallis test). However, on the multivariate test two factors, namely half value layer of the X-ray beam and (CBT), had a significant effect on MGD per woman (p<0.05). No significant relationships were seen between MGD per woman with respect to ethnicity, body mass index or age.
Epidermal inclusion cyst (EIC) arising from the breast is an uncommon benign condition. We report two cases of enlarging EIC of the breast in two women in their forties. The diagnosis of this condition may not be straightforward with imaging alone if an EIC presents as an enlarging lump in the breast and mimics a benign breast lesion, most commonly a fibroadenoma or malignant lesion with benign imaging features. Excision is usually recommended for a definite histopathological diagnosis and for the prevention of potential risks of malignant transformation. Asymptomatic stable lesions do not require treatment; biopsy is unnecessary, and follow-up imaging suffices if typical sonographic and clinical findings are found.
INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.