Fine needle aspiration of benign and malignant breast masses associated with pregnancy.

Of 1,612 fine needle aspirates (FNA) of breast lesions performed over a seven-year period, 25 cases (1.5%) were identified as breast masses associated with pregnancy. Patients ranged in age from 16 to 46 years, with a mean of 27. Gestational age at the time of FNA ranged from three months to three months postpartum or following breast-feeding. Cytologic diagnoses of these pregnancy-associated breast masses were: galactocele (5 cases, 20%), lactating adenoma (9 cases, 36%), fibroadenoma with lactational change (7 cases, 28%), juvenile fibroadenoma with lactational change (1 case, 4%), atypical reactive duct cells with lactational change (1 case, 4%) and infiltrating duct carcinoma (2 cases, 8%). The degree of lactational change varied proportionately with gestational age. None of the 22 patients with benign cytologic diagnoses of galactocele, lactating adenoma or fibroadenoma subsequently developed carcinoma. The mean clinical follow-up for these 22 patients was 27 months. Three cases of fibroadenoma and the case of juvenile fibroadenoma were confirmed by surgical excision. Biopsy of the lesion cytologically diagnosed as atypical reactive duct cells with lactational change revealed infiltrating duct carcinoma (IDC). All three patients with IDC had involvement of multiple axillary lymph nodes, and 1 patient had widely metastatic disease. In two cases of IDC the background lactational breast epithelium exhibited marked cytologic atypia that closely resembled the IDC. Pregnancy-related cellular atypia potentially results in a false-positive diagnosis of breast carcinoma on FNA. FNA is useful in distinguishing benign breast masses of pregnancy from those with marked cytologic atypia requiring surgical biopsy and may minimize the delayed diagnosis of carcinoma associated with pregnancy.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression

OBJECTIVE: To study the relationship of cell death and proliferation to histologic grade and p53 expression in invasive carcinoma of the breast. STUDY DESIGN: A total of 31 cases of infiltrating duct carcinoma of the breast were randomly selected. The terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) reaction and p53 immunostaining were performed on representative paraffin-embedded tissue sections. Mitotic and apoptotic indices (MI and AI) were also measured on hematoxylin-eosin-stained sections. Histologic grade of infiltrating duct carcinoma was performed with the help of the Nottingham modification of the Bloom-Richardson system. Tumor grade and p53 overexpression were correlated with MI, AI and AI detected by TUNEL. RESULTS: There were a total of 31 infiltrating duct carcinomas of the breast, of which 13 cases were grade 1 and nine cases each were grade 2 and 3. Cells with positive TUNEL showed a strong brown nuclear positivity. TUNEL showed positivity from the periphery of the nuclear margin to the central portion. AI detected by TUNEL did not correlate with tumor grade (ANOVA, P > .05). MI was significant only in grade 1 versus grade 3 and 2 versus grade 3 carcinomas (ANOVA, P < .01). The morphologic apoptotic index was significant only in grade 1 versus grade 3 carcinomas. Nine cases showed p53 overexpression, and the rest of the cases were negative for p53 immunostaining. MI, AI and TUNEL were not significantly different in p53-negative and -positive groups. Pearson's correlation coefficient showed that AI and MI were significantly related, but there was no significant relation between AI detected by TUNEL and MI. CONCLUSION: MI is still more useful than AI or AI detected by TUNEL in differentiating various grades of carcinoma of the breast.     

B超引导下乳腺肿块粗针穿刺诊断的分析（附120例报道）

目的：探讨B超引导下粗针穿刺在乳腺肿块诊断中的应用意义。方法：使用B超引导下粗针吸取穿刺对120例乳腺肿块进行穿刺活检,然后进行固定,脱水,染色,镜检,结合临床作出病理学诊断。结果：粗针穿刺诊断包括良性病变48例,非典型性导管上皮增生（ADH）32例,导管内癌12例,浸润性癌28例。与后续手术标本病理诊断比较得出确诊率,其中良性病变的诊断率为95．83％（46／48）,ADH的确诊率为75％（24／32）,导管内癌的确诊率为58．33％（7／12）,浸润性癌诊断率为92．86％（26／28）,其中导管内癌与浸润性导管癌和乳腺良性病变的确诊率有显著性差异,而ADH与浸润性导管癌和乳腺良性病变间的确诊率有差异,但本组数据没有统计学意义。结论：超声引导下粗针穿刺对乳腺浸润性癌和良性病变的诊断率较高,但对ADH和原位癌的确诊率较低,有待进一步改进。     

The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast

S. Samanta, P. Dey and R. Nijhawan The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast Aims and objectives: Micronucleus (MN) scoring was carried out in benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) breast lesions to evaluate the role of MN as a biomarker in breast carcinomas. We also compared MN scores among different cytological grades of breast carcinoma. Materials and methods: A total of 31 archival cases of fibroadenoma (FA) and 40 cases of infiltrating ductal carcinoma (IDC) were selected. The best May‐Grünwald–Giemsa (MGG) stained fine needle aspiration cytology (FNAC) smear of each case was selected. The MN scoring was carried out independently by two observers on 1000 epithelial cells in oil immersion magnification (100× objective). The MN scores in FA and IDC were compared. The IDC cases were graded and the MN scores in different cytological grades of IDC were compared. Results: The mean MN scores (± standard deviation) in FA and IDC were 0.6 (± 1.1) and 13.6 (± 12.8), respectively, which were significantly different (P < 0.0001). There were seven grade 1, 13 grade 2, and 20 grade 3 IDCs. The mean MN scores (± standard deviation) of grade 1, 2 and 3 IDC were 4.3 (± 2.3), 11.95 (± 9.2) and 21.1 (± 16.7), respectively. An analysis of variance (anova ) test showed a significant difference in MN score between all the grades of IDC (P < 0.05). However, there was no significant difference between fibroadenoma and grade 1 IDC. The Pearson’s correlation coefficient showed positive correlations between MN scoring in the different grades of IDC. Conclusions: MN scoring on routinely stained smears of IDCs was significantly higher than in fibroadenoma and was relatively easy, reliable and reproducible. As MN scoring of grade 1 IDC was similar to fibroadenoma, a larger study should be conducted to compare grade 1 IDC with other benign breast lesions.     

Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast

Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.     

Automated image morphometry of lobular breast carcinoma

OBJECTIVE: To analyze the role of automated image morphometry (AIM) in distinguishing infiltrating lobular carcinoma (ILC) of the breast from benign, borderline and infiltrating ductal carcinoma (IDC). STUDY DESIGN: Only histopathologically proven lobular carcinoma, ductal carcinoma, borderline lesions and benign breast lesions were selected for the study. There were 19 cases of ILC and 30 cases of IDC, 20 cases of benign lesions (fibroadenoma, 18; fibrocystic disease, 1; and fibroadenosis, 1); 10 cases were borderline lesions (mild epithelial hyperplasia, 3; moderate epithelial hyperplasia, 2; florid epithelial hyperplasia 4; intraductal papillary carcinoma, 1). In all cases hematoxylin and eosin-stained slides were used for AIM. At least 100 cells from each case were subjected to analysis randomly with an image cytometer with Leica Quantimet 600 software (Cambridge, England). Nuclear area, diameter, perimeter, convex perimeter, convex area and roundness were measured in each case with random, unbiased selection of cells and 40 x objectives (one pixel = 0.46 microm). AIM data on the cases were analyzed in relation to final cytologic diagnosis. RESULTS: All the nuclear morphometric features of ILC were much lower than those of IDC and borderline lesions, whereas nuclear morphometric data on ILC were only marginally more than those on benign cases. ANOVA showed that mophometric data were significant (P < .05) in all the variables between ILC and IDC. However, there was no significant difference between ILC, and borderline and benign cases. CONCLUSION: Image morphometry may be useful in distinguishing ILC from IDC on cytologic smears. However, morphometric data may not be helpful in distinguishing benign and borderline lesions from ILC.     

Fine needle aspiration cytology of lobular breast carcinoma. Comparison with other breast lesions

OBJECTIVE: To analyze the detailed cytomorphology of lobular breast carcinoma and to compare the cytologic smears of benign, borderline and infiltrating duct carcinoma. STUDY DESIGN: Fine needle aspiration cytology (FNAC) smears of histopathologically proven infiltrating lobular carcinoma (ILC), infiltrating ductal carcinoma (IDC), borderline lesions and benign breast lesions were selected for study. Detailed cytomorphologic analysis of the smears was carried out on hematoxylin and eosin- and May-Grünwald-Giemsa--stained slides, and a comparison of results was done. The various cytologic features were also graded semi-quantitatively with the numerical score; logistic regression analysis was done. RESULTS: There were 25 cases of ILC, 30 of IDC, and 10 borderline and 18 benign lesions. Cytologic diagnosis of malignancy on FNAC smears of ILC was offered in 19 cases; of them, 2 cases were diagnosed as ILC. The remaining six cases were diagnosed as borderline (four) and benign lesions (two). Overall sensitivity in detection of malignancy in ILC cases was 76%. FNAC smears of ILC showed moderate (52%) to abundant (32%) cellularity. The cells of ILC were arranged both in clusters and in dissociation (72%). Individual cells were monomorphic (40%) to mildly pleomorphic (60%), and the cells were smaller. The cells showed a smooth, regular nuclear margin; bland chromatin; and indistinct nucleoli. Indian file arrangement was frequently observed (28%). Nuclear molding (28%) and intranuclear inclusions (16%) were also noted. Intracytoplasmic lumina were seen in occasional cases. Logistic regression analysis was carried out, and a comparison between lobular carcinoma and ductal carcinoma, and borderline and benign lesions was done. Logistic regression analysis of cytomorphologic features showed that cellularity and nuclear margin irregularities were the two most important features to distinguish ILC from IDC. In comparison to borderline lesions, cell dissociation was more common in ILC. The salient cytologic features that helped to distinguish ILC from benign lesions was cell size, cellularity, cell uniformity and chromatin pattern. CONCLUSION: There are overlapping cytologic features between ILC, IDC and borderline breast lesions on FNAC smears. Logistic regression analysis may be helpful in this regard.     

Nuclear image morphometry and cytologic grade of breast carcinoma

OBJECTIVE: To correlate visual cytologic grade with automated nuclear morphometry of carcinoma of the breast. STUDY DESIGN: We randomly selected 24 histologically proven infiltrating ductal carcinomas of the breast and 10 benign breast lesions (fibroadenoma). Hematoxylin-eosin-stained fine needle aspiration cytology (FNAC) smears were selected for both cytologic grade and automated image morphometry. The same hematoxylin-eosin-stained FNAC smears were studied for area, convex area, standard deviation of nuclear area, diameter, perimeter and convex perimeters of nucleus. At least 100 cells from each case were measured with an image cytometer. RESULTS: Mean nuclear area, standard deviation of nuclear area, nuclear diameter, convex area, convex perimeter and perimeter were significantly increased from benign versus grade 1 carcinomas and grade 1 versus grade 2 and 3 carcinomas (one way ANOVA test). However, there was no significant difference in grade 2 versus grade 3 carcinomas. CONCLUSION: Automated image cytometry rapidly and successfully measures various nuclear parameters. The measurement of various nuclear parameters would be helpful in future applications of automated diagnosis and grading of breast carcinomas from cytologic material.     

Immunohistochemical localization of sex hormone-binding globulin in normal and neoplastic breast tissue.

The distribution of sex hormone-binding globulin-like antigens (SHBG-LA) in normal and neoplastic human breast tissues was investigated by immunohistochemistry, employing a monospecific polyclonal antiserum against highly purified human SHBG and an avidin-biotin-peroxidase complex (ABC) method in formalin-fixed paraffin embedded tissue sections. In normal breast tissues the staining of SHBG-LA was present exclusively in the cytoplasm of epithelial cells of ductal and ductular types. Nuclei as well as stromal and lymphatic tissues remained unstained. While the staining was positive in all cases of intraductal carcinoma, only 4 out of 15 infiltrating carcinomas revealed SHBG-LA. The demonstration of a plasma sex steroid binding globulin in the cytoplasm of endocrine target cells is consistent with the hypothesis that steroid-binding globulins are able to enter target cells. The apparent loss of this specific cell function in infiltrating carcinomas may result from dedifferentiation and change of cell membrane properties occurring during the process of neoplastic progression.     

Consistent lack of CD34-positive stromal cells in the stroma of malignant breast lesions

To examine the distribution of CD34-positive and ASMA-positive stromal cells in various breast lesions, we performed immunohistochemical assays (using a streptavidin-biotin immunoperoxidase technique) of tissue specimens, obtained by excisional biopsy and partial or total mastectomy, from 62 patients with breast lesions. Specimens were obtained from 64 lesions as follows: fibrocystic disease (n=12), intraductal papilloma (n=4), fibroadenoma (n=17), invasive lobular carcinoma (n=6), invasive ductal carcinoma (n=20) and invasive micropapillary carcinoma (n=5). In normal breast tissue (controls), CD34-positive spindle cells were abundant in the intralobular stroma, but no ASMA-positive stromal cells were identified except myoepithelial cells. Small to large numbers of CD34-positive cells were observed in the stroma of 29 of 33 benign diseases. In all invasive carcinomas (lobular, ductal and micropapillary), no CD34-positive stromal cells were observed in the stroma. In the stroma of benign lesions, the number of ASMA-positive stromal cells was various, but the stroma of all invasive breast cancers contained ASMA-positive stromal cells. The present results indicate that disappearance of CD34-positive stromal cells consistently occurs in the stroma of invasive carcinoma of the breast, irrespective of histological type and may be associated with the presence of ASMA-positive stromal cells.     

乳腺癌组织中FOXO1蛋白表达与细胞增殖和细胞凋亡的相关性

目的研究乳腺癌组织中FOXO1蛋白表达与细胞增殖和细胞凋亡的相关性。方法利用免疫组织化学技术检测60例乳腺浸润性导管癌、21例导管内癌、30例导管内乳头状瘤及15例正常乳腺组织中FOXO1、Ki-67及活化Caspase-3蛋白的表达。结果FOXO1及活化Caspase-3蛋白在乳腺浸润性导管癌和导管内癌中的阳性表达率和阳性表达强度均显著低于导管内乳头状瘤和正常乳腺组织。Ki-67蛋白在乳腺浸润性导管癌和导管内癌中的阳性表达率和阳性表达强度均显著高于导管内乳头状瘤和正常乳腺组织;浸润性导管癌中FOXO1、Ki-67及活化Caspase-3的表达强度与癌组织的病理学分级无关;在浸润性导管癌、导管内癌、导管内乳头状瘤及正常乳腺组织中,FOXO1蛋白的表达强度与Ki-67呈显著负相关,而与活化Caspase-3的表达强度呈显著正相关。结果 FOXO1蛋白的表达下调可能与乳腺导管癌的发生密切相关;该蛋白可能是一种细胞增殖的负性调节因子,同时亦是一种细胞凋亡促进因子,FOXO1基因有可能成为乳腺浸润性导管癌基因治疗的有效靶点。     

Fine needle aspiration cytopathology of phyllodes tumor. Differential diagnosis with fibroadenoma

The differential diagnosis of benign or borderline phyllodes tumors of the breast in fine needle aspiration biopsy smears was studied. Smears from five histologically proven cases and 20 proven cases of fibroadenoma were evaluated with regard to their cytologic features. The findings indicate that the presence of a high cellularity of stromal fragments (including bipolar naked nuclei), clusters of hyperplastic ductal cells and giant cells and the absence of apocrine metaplasia may suggest a diagnosis of phyllodes tumor, as opposed to fibroadenoma. The borderline phyllodes tumor showed a sarcomatous atypia and/or small intranuclear cytoplasmic invaginations in some cells. The differential diagnosis of this tumor with malignant phyllodes tumor and plasma-cell mastitis is also discussed.     

Mammary radioiodine accumulation due to functional sodium iodide symporter expression in a benign fibroadenoma

The sodium iodide symporter (NIS) has been characterized to mediate the active transport of iodide not only in the thyroid gland but also in various non-thyroidal tissues, including lactating mammary gland and the majority of breast cancers, thereby offering the possibility of diagnostic and therapeutic radioiodine application in breast cancer. In this report, we present a 57-year-old patient with multifocal papillary thyroid carcinoma, who showed focal radioiodine accumulation in a lesion in the right breast on a posttherapy (131)I scan following radioiodine therapy. CT and MR-mammography showed a focal solid lesion in the right breast suggestive of a fibroadenoma, which was confirmed by histological examination. Immunostaining of paraffin-embedded tumor tissue sections using a human NIS antibody demonstrated NIS-specific immunoreactivity confined to epithelial cells of mammary ducts. In conclusion, in a thyroid cancer patient we identified a benign fibroadenoma of the breast expressing high levels of functionally active NIS protein as underlying cause of focal mammary radioiodine accumulation on a posttherapy (131)I scan. These data show for the first time that functional NIS expression is not restricted to lactating mammary gland and malignant breast tissue, but can also be detected in benign breast lesions, such as fibroadenomata of the breast.     

Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer

Background

Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images.

Methods

hNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images.

Results

Staining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p = 0.0033, CI = 95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2–ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method.

Conclusion

The study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted ¹³¹I radio-ablative therapy is aimed.     

The malignant potential of HIV-associated Kaposi sarcoma

Background

Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.

Methods

S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.

Results

S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.

Conclusion

S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.     

Cytofluorometric nuclear DNA content analysis of breast tissues after frozen section diagnosis

OBJECTIVE: To establish a suitable method for measurement of nuclear DNA content in breast tissues from frozen storage after frozen section diagnosis. STUDY DESIGN: For fundamental research, rat liver samples preserved in a deep freezer were used. Four protocols were used (1. fixation with 70% ethanol followed by naked nuclei preparation; 2. fixation with 10% neutral buffered formalin followed by naked nuclei preparation; 3. preparation for naked nuclei prior to fixation with 70% ethanol; and 4. preparation for naked nuclei prior to fixation with 70% neutral buffered formalin). For clinical research, 13 separate fresh frozen breast tissue samples were analyzed after frozen section diagnosis. One contained a malignant phyllodes tumor (MPT) consisting of 2 components, benign epithelial cells and malignant stromal cells; 3 were benign tumors containing fibroadenoma; and 9 cases were carcinomas, consisting of 5 scirrhous, 3 papillotubular and 1 mucinous. RESULTS: Protocols 1, 2 and 3 were not suitable methods for our purpose because remaining cytoplasm or cohesive nuclei were observed. In protocol 4 the cytoplasm was completely undetectable, and nuclei were suitably separated for nuclear DNA content measurement. Benign epithelial cell component nuclei presented a diploid pattern, and the malignant stromal cell component nuclei indicated a euploid pattern in MPT. All 3 cases of benign constituents in fibroadenoma showed a diploid pattern, as did the 3 carcinoma cases (1 mucinous, 1 scirrhous and 1 papillary). Four scirrhous and 2 papillary carcinomas showed an aneuploid pattern. CONCLUSION: Our findings show that it is possible to measure nuclear DNA content of human frozen storage tissues after frozen section diagnosis.     

乳腺内不可触及病灶的定位活检应用价值

目的:探讨乳腺内不可触及病灶(NPBL)的定位活检技术及其在乳腺癌早期诊断中的临床应用价值。方法:对彩超发现的4459个和钼靶发现的25个NPBL分别行麦默通旋切和钩丝定位活检,确定病灶的病理类型。结果:4459个NPBL中3196个病灶为乳腺腺病或伴纤维腺瘤样结节(71.7%),1198个为纤维腺瘤(26.9%),11个为分叶状肿瘤(0.2%),17个为导管内乳头状瘤(0.4%),9个为乳腺导管原位癌,5个为导管原位癌伴微浸润,23个为浸润性癌(恶性占0.8%)。25个钼靶发现的NPBL中乳腺腺病13例(52%),导管原位癌7例,导管原位癌伴微浸润2例,浸润性癌3例(恶性占48%)。结论:超声引导下麦默通和钼靶引导下钩丝定位切除可以对NPBL做出定性诊断,具备创伤小、手术时间短和定位精准等特点,对提高乳腺癌的早期诊断率、降低死亡率具有一定的临床应用价值。     

Diagnostic significance of 'benign pairs' and signet ring cells in fine needle aspirates (FNAs) of the breast

sturgis c. d., sethi s., cajulis r. s., hidvegi d. f. and yu g. h. (1998) Cytopathology 9, 308–319 Diagnostic significance of ‘benign pairs’ and signet ring cells in fine needle aspirates (FNAs) of the breast Most breast mass lesions are readily characterized by FNA with cytodiagnosis. Occasionally, benign but markedly proliferative lesions are diagnostically difficult to separate from well differentiated malignancies. We present information pertaining to the diagnostic significance of two cytologic findings observed in breast aspiration specimens, namely pairs of stripped bipolar nuclei and signet ring cells (SRC). We have evaluated aspirate smears from 219 cases of histologically proven benign (n= 114) and malignant (n= 105) breast lesions. Both singlets and pairs of bipolar nuclei and SRC were enumerated, and their numbers were correlated to histological diagnosis. Closely associated pairs of stripped bipolar nuclei were found in 68% of benign lesions compared with only 3.8% of carcinomas, establishing their presence as a highly specific indicator of a benign process. Large numbers of such ‘benign pairs’ also favoured the diagnosis of fibroadenoma. SRC were identified in 66% of histologically proven carcinomas (67% of ductal and 70% of lobular). SRC were also present in 10% of histologically benign cases. In the malignant cases, SRC were most frequently noted in a single cell distribution or within small, loosely cohesive tissue fragments. In the benign instances, SRC were most commonly noted within large fragments, and many of these cells were proved by immunohistochemical reactions to be vacuolated myoepithelial cells. We conclude that the presence of bipolar nuclei in closely associated pairs suggests benignity and aids in the subclassification of benign breast masses. In addition, the presence of SRC does not aid in the classification of tumour subtype (ductal vs lobular), and the occurrence of such cells in the proper context should prompt surgical biopsy.     

Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer

To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.