Missed cancers on mammograms: causes and measures of prevention.

Mammographically missed breast cancers remain a major medical and legal issue. In order to clarify causes and methods of the limitations, we present the experience of our Unit on this field. During the years 1999 and 2000, 319 breast cancer patients were admitted for surgical treatment to our Unit. Their files were reviewed in order to identify cases with mammography-related delayed diagnosis. Thirty-three cases of mammographically missed cancers were found (10.3%). The usual reasons for the delayed diagnoses were: retrospectively visible cancers, in benign looking lesions no further action was taken, and lesions with a rather malignant appearance were reported as benign. Missed cancers could be reduced by simple measures such as the full assessment of breast patients with clinical, radiologic, and cytologic-histologic evaluation, the double screening of mammograms, and improvement of the mammographic equipment and technique.

Carcinosarcoma of the breast: report of two cases.

Carcinosarcoma is a rare, malignant tumor of the breast, consisting of intraductal or infiltrating carcinoma contiguous or subtly merged with a highly cellular, mitotically active pleomorphic spindle cell stroma (sarcoma). It is a form of the metaplastic mammary carcinomas and it is probably derived of myoepithelial cells. We report two cases of breast carcinosarcoma in two white women. The patients, following a frozen section positive for malignancy, had had a modified radical mastectomy. Paraffin sections and positive immunohistochemical cell staining (in our first case) confirmed the diagnosis of carcinosarcoma. This tumor should be distinguished from other forms of metaplastic carcinomas because it is very aggressive and has an ominous prognosis.

Computer-aided preoperative diagnosis of microcalcifications on mammograms.

PURPOSE: To evaluate of a computer-aided method for differentiating malignant from benign clustered microcalcifications. MATERIAL AND METHODS: Our material was 350 suspicious microcalcifications on mammograms from 330 female patients who underwent breast biopsy (after hook wire localization and under mammographic guidance). The histologic findings were malignant in 140 cases (40%) and benign in 210 cases (60%). Those clusters were manually detected, computer-aided analyzed and quantitatively estimated. Besides computer analysis, 3 physicians-observers (2 radiologists and 1 breast surgeon) evaluated the malignant or benign nature of the clustered microcalcifications. The performance of the artificial network, each observer and the three observers as a group was evaluated by receiver operating characteristics (ROC) curves. RESULTS: Comparison of the ROC curves revealed the following AUC values (area under the curve): computer - 0.950, physician 1 - 0.815, physician 2 - 0.830, physician 3 - 0.830, and physicians as a group - 0.825. The results, compared by the student t-test for paired data, showed a statistically significant difference between computer analysis and physicians' performance, independently and as a group. CONCLUSION: Our study showed that computer analysis achieved statistically significantly better performance than that of physicians in the classification of malignant and benign calcifications.

Pre-operative Tc-99m-sestamibi scanning and intra-operative nuclear mapping: are they accurate in localizing parathyroid adenomas?

PURPOSE: Presentation of the results of Tc-99m-sestamibi imaging in the pre-operative localization of parathyroid adenomas and the intra-operative localization of those lesions using a gamma detector (prospective study). PATIENTS & METHODS: Eighteen consecutive patients aged 27-75 years with primary hyperparathyroidism (PHPT) underwent Tc-99m-sestamibi scanning 1-2 hours before the operation and the presence of a single adenoma was recognized. All our patients underwent bilateral neck exploration based on pre-operative scanning and intra-operative gamma detector guidance and the adenoma was detected in the positions shown by both methods. RESULTS: In 16 patients we found a single adenoma localized in the same position shown by pre-operative scanning, while the intra-operative method accurately revealed all abnormal glands. In one of the two patients where an inaccurate pre-operative localization technique had been carried out, we performed thyroid lobectomy (the adenoma proved to be intrathyroidal), while the other one had an adenoma which was not close to the site indicated by the pre-operative scintigraphy. Serum calcium reverted to normal within a few days postoperatively. CONCLUSION: Patients with true-positive scans for single parathyroid adenoma could be eligible for minimally invasive operations since the abnormal gland is easily identified by the above-mentioned methods.

Granular cell tumor of the breast: a rare lesion resembling breast cancer.

Granular cell tumor (GCT) is an uncommon, usually benign tumor that occasionally involves the breast. It is possibly of neural origin (Schwann cells) and usually occurs in premenopausal black women. Physical examination, mammographic, ultrasonographic findings and pathologic examination may suggest breast malignancy. Positive immunohistochemical staining of the cells for S-100 protein, NSE, and CEA is indicative of GCT. Surgical treatment of choice is wide local excision. We report a case of granular cell tumor of a female breast. A 52-yr-old white woman had a palpable mass close to her right axilla. Computer tomography (CT) showed a 3.74 cm mass in the mammary tail of Spencer. The findings were suspicious for malignancy and the lesion was widely resected. Pathologic examination showed granular cell tumor.

Autoimmune thyroid disease in women with breast carcinoma.

AIMS: Estimation of prevalence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS: The prevalence of autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. RESULTS: Autoimmune thyroiditis was found in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). CONCLUSIONS: There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage.

Use of artificial neural networks (computer analysis) in the diagnosis of microcalcifications on mammography.

INTRODUCTION/OBJECTIVE: The purpose of this study was to evaluate a computer based method for differentiating malignant from benign clustered microcalcifications, comparing it with the performance of three physicians. METHODS AND MATERIAL: Materials for the study are 240 suspicious microcalcifications on mammograms from 220 female patients who underwent breast biopsy, following hook wire localization under mammographic guidance. The histologic findings were malignant in 108 cases (45%) and benign in 132 cases (55%). Those clusters were analyzed by a computer program and eight features of the calcifications (density, number, area, brightness, diameter average, distance average, proximity average, perimeter compacity average) were quantitatively estimated by a specific artificial neural network. Human input was limited to initial identification of the calcifications. Three physicians-observers were also evaluated for the malignant or benign nature of the clustered microcalcifications. RESULTS: The performance of the artificial network was evaluated by receiver operating characteristics (ROC) curves. ROC curves were also generated for the performance of each observer and for the three observers as a group. The ROC curves for the computer and for the physicians were compared and the results are:area under the curve (AUC) value for computer is 0.937, for physician-1 is 0.746, for physician-2 is 0.785, for physician-3 is 0.835 and for physicians as a group is 0.810. The results of the Student's t-test for paired data showed statistically significant difference between the artificial neural network and the physicians' performance, independently and as a group. DISCUSSION AND CONCLUSION: Our study showed that computer analysis achieves statistically significantly better performance than that of physicians in the classification of malignant and benign calcifications. This method, after further evaluation and improvement, may help radiologists and breast surgeons in better predictive estimation of suspicious clustered microcalcifications and reduce the number of biopsies for non-palpable benign lesions.

Breast cancer in ectopic breast tissue.

Ectopic breasts usually develop along the mammary ridges. Their incidence has been reported as up to 5-6%. Development of malignancy is rare. We report three cases of postmenopausal female patients with breast cancer which developed in the axillary accessory breast. They were all successfully treated by surgery and adjuvant therapy. A review of the literature on the incidence and pathology of ectopic mammary tissue is also presented.

Alterations of the 16q22.1 and 16q24.3 chromosomal loci in sporadic invasive breast carcinomas: correlation with proliferative activity, ploidy and hormonal status of the tumors.

BACKGROUND: Breast cancer is characterized by complex genetic alterations found in multiple chromosomal regions, most commonly losses of 17p, 16q, 8p and others. A number of tumor suppressor genes mapped on these loci have been investigated in mammary tumors, whereas other gene products are of unclear function and await identification. MATERIALS AND METHODS: We analyzed the loss of heterozygosity (LOH) of two chromosomal loci: a. 16q24.3 using the genetic markers D16S303, D16S3026 and D16S3407 and b. 16q22.1, the locus of E-cadherin gene, using the microsatelite markers D16S503, D16S752 and D16S512, in a series of 63 sporadic invasive breast carcinomas consisting of 56 ductal, 4 lobular and 3 tumors of mixed type. Our findings were correlated with proliferative activity, ploidy and hormonal status of the tumors. RESULTS: Fourteen (22.2%) tumors demonstrated LOH of 16q24.3. Allelic imbalance of the 16q22.1 locus was found in 19 of 61 informative cases (31%) and commonly coexisted with LOH of 16q24.3. A significant association was observed between LOH of D16S752 and the absence of progesterone receptors in tumor cells (p = 0.005). CONCLUSIONS: LOH of 16q24.3 and 16q22.1 are frequent genetic alterations in breast cancer and they do not seem to correlate with tumor cell proliferation or ploidy. The statistical association between LOH of 16q24.3 and progesterone receptors need to be further investigated in larger series.

Central venous and mixed venous oxygen saturation in critically ill patients.

BACKGROUND: Although mixed venous O2 saturation (SvO2) accurately indicates the balance of O2 supply/demand and provides an index of tissue oxygenation, the use of a pulmonary artery (PA) catheter is associated with significant costs, risks and complications. Central venous O2 saturation (ScvO2), obtained in a less risky and costly manner, can be an attractive alternative to SvO2. OBJECTIVES: To investigate whether the values of ScvO2 and SvO2 are well correlated and interchangeable in the evaluation of critically ill ICU patients and to create an equation that could estimate SvO2 from ScvO2. METHODS: Sixty-one mechanically ventilated patients were catheterized upon admission and ScvO2 and SvO2 values were simultaneously measured in the lower part of the superior vena cava and PA respectively. RESULTS: SvO2 was 68.6 +/- 1.2% (mean +/- SEM) and ScvO2 was 69.4 +/- 1.1%. The difference is statistically significant (p < 0.03). The correlation coefficient r is 0.945 for the total population, 0.937 and 0.950 in surgical and medical patients, respectively. In 90.2% of patients the difference was <5%. When regression analysis was performed, among 11 models tested, power model [SvO2 = b0(ScvO2)b1] best described the relationship between the two parameters (R2 = 0.917). CONCLUSIONS: ScvO2 and SvO2 are closely related and are interchangeable for the initial evaluation of critically ill patients even if cardiac indices are different. SvO2 can be estimated with great accuracy by ScvO2 in 92% of the patients using a power model.

Factors affecting axillary lymph node metastases in patients with T1 breast carcinoma.

The purpose of this study was to determine factors associated with the incidence of axillary lymph node metastases (ALNM) in T1 tumors and cases in which axillary dissection could be omitted. Data from 195 patients with T1 primary invasive breast cancer (size < or = 2 cm) who underwent either mastectomy or wide local excision of the tumor and axillary dissection were reviewed. ALNM was found in 59 of 195 patients with T1 tumors (30.3%). Tumor size was found to be the only independent predictor of ALNM, having a directly analogous relationship with the probability of invaded nodes: T1a (< or = 5 mm) tumors had 0 per cent ALNM, whereas T1b (5 mm < T1b < or = 10 mm) and T1c (10 mm < T1c < or = 20 mm) tumors had 25.7 per cent and 33.8 per cent ALNM respectively. Among the other factors studied (patient age, tumor site, hormone receptor status, histologic type, and grade of the tumor) only the histologic grade of the tumor cells appeared to correlate with the incidence of lymph node involvement, but this was not statistically significant. In conclusion only tumor size has statistically significant correlation with the incidence of ALNM. Routine axillary dissection could be omitted only in patients at minimal risk of ALNM (ductal carcinoma in situ and T1a) and when treatment decisions were not influenced by lymph node status (e.g., elderly patients with clinically negative axilla). Axillary dissection (at least levels I and II) should be performed in all cases with primary invasive breast cancer with tumor size > 5 mm.

p53 protein expression and proliferative activity in ductal breast carcinomas.

The immunocytochemical expression of p53 protein and Ki-67 labelling index in tumour cells of 100 ductal breast carcinomas of different histological grade and stage was evaluated in cytological material. In order to investigate p53 expression and Ki-67 expression an avidin-extravidin immunocytochemical technique was applied to imprints. Monoclonal antibody (MoAb) DO-p53 and proliferating cell monoclonal antibody were used as primary antibodies. A statistically significant difference was observed between p53 protein expression and grade of malignancy and clinical stage (P = 0.001, P < 0.001, respectively). A statistically significant difference was also observed between Ki-67 LI and histological grade and stage of the tumours (P < 0.001, P < 0.001 correspondingly). A correlation was observed between p53 protein expression and Ki-67 LI (P < 0.001). The immunocytochemical study of p53 protein and Ki-67 expression in cytological material represents a simple method which can be applied in routine cytological laboratories for the investigation of potential malignancy of ductal breast cancer.

Changes of the infrarenal aortic segment after conventional abdominal aortic aneurysm repair.

OBJECTIVES: to delineate the natural history of the residual infrarenal aortic segment after conventional abdominal aortic aneurysm (AAA) repair. DESIGN: open prospective study. PATIENTS AND METHODS: between 1990 and 1997, 100 patients, who underwent conventional infrarenal AAA repair at our department, were followed annually by means of colour duplex ultrasonography. Data from 76 patients who had at least 3 scans were analysed. RESULTS: mean duration of follow-up was 4.7 years (range: 3-8 years). The residual infrarenal aorta dilated a mean of 0.57 mm annually. No patient required reoperation. There was no significant correlation between dilatation and any of the recorded risk factors except for the initial neck diameter (p=0.03). CONCLUSIONS: conventional AAA surgery is durable so that surveillance, during the first 5 postoperative years, is not justified in terms of cost-effectiveness. The impact of such a dilatation on endovascular AAA repair requires further investigation.

Internal carotid artery stenosis: rate of progression.

OBJECTIVES: to assess the incidence and the rate of progression of internal carotid artery (ICA) stenosis and to determine the related risk factors. DESIGN: open prospective study. MATERIALS AND METHODS: between 1988-1997, 442 carotid arteries with various degrees of stenosis were followed using colour duplex ultrasonography every 6 months. Of these arteries, 290 (66%) were asymptomatic, 62 (14%) had caused transient ischaemic attack and 90 (20%) a stroke. In 145 cases (33%), there was concomitant coronary artery disease (CAD), in 134 (30%) diabetes mellitus, in 248 (56%) hypertension, in 139 (31%) hypercholesterolaemia and in 370 (84%) history of smoking. Of the plaques, 44 (10%) were uniformly echolucent, 19 (4%) haemorrhagic, 136 (31%) predominantly echolucent, 146 (33%) predominantly echogenic and 97 (22%) uniformly echogenic. RESULTS: significant progression of stenosis occurred in 82 cases (19%). The mean progression rate in these cases was 15% annually (range: 5-50%). There was no statistically significant correlation between the progression of the ICA stenosis and initial neurological status, age, gender, diabetes mellitus, hypertension, hypercholesterolaemia and smoking habit. Stenosis progression was correlated only with CAD and the ultrasonographic characteristics of the plaques. Patients with CAD as well as those with uniformly echolucent plaques presented a higher incidence and rate of stenosis progression (p<0.05). CONCLUSIONS: progression of internal carotid artery stenosis occurred in 19% of cases. The mean progression rate in these patients was 15% annually and was correlated with CAD and the ultrasonographic characteristics of the plaque.

Aneurysms of the distal branches of the external carotid artery.

Aneurysms of the distal branches of the external carotid artery are rare and usually traumatic in origin. We present two cases which were treated in our clinic. The first case is about a traumatic aneurysm of the left superficial temporal artery (STA) in a young boy 8 years old. The young patient developed a pulsatile mass above his left eyebrow ten days after a bite by a boy of the same age. The second case is referred in a 36-year old woman with a pulsatile mass behind the right ear, which was an aneurysm of the posterior auricular artery. The treatment was ligation and resection under local anesthesia in the first case and under general anesthesia in the latter. Surgeons' familiarity with this entity is important for diagnosis and treatment.

Role of malignancy and preoperative embolization in the management of carotid body tumors.

The purpose of this retrospective study is to present our approach to the management of patients with carotid body tumors (CBTs), emphasizing the role of malignancy and preoperative embolization. Between 1975 and 1998 a series of 18 patients with CBTs were treated, and 16 of them underwent successful excision of the tumor. According to the Shamblin classification, six of the tumors were type I, six type II, and six type III. In three of these patients (two with type II tumors and one with type III) in whom preoperative embolization had been performed, mean intraoperative blood loss was 400 ml, whereas in the remaining 13 cases this loss was 700 ml. Two patients with intracranial tumor spread underwent only radiotherapy. Neither postoperative deaths nor strokes occurred. Temporary cranial nerve injury occurred in four cases (25%). Local lymph node invasion was found in two patients, establishing the diagnosis of malignancy. One of these patients developed distal metastases 3 years after the operation and was treated with radiotherapy and octreotide. Follow-up ranging from 30 months to 23 years (mean 5 years) revealed no local recurrence except for the two patients who were treated with radiotherapy only. In conclusion, surgical excision remains the treatment of choice for CBTs and can be performed without major risks and with low morbidity and mortality. Preoperative embolization is helpful by diminishing intraoperative bleeding, and malignancy, though rare justifies early management.

Carcinosarcoma of the submandibular salivary gland.

We report a rare case of submandibular salivary gland carcinosarcoma ('true' malignant mixed tumour) which occurred in a 77-year-old man. Microscopic examination showed a neoplasm comprised of sarcomatous elements (chondrosarcoma, rhabdomyosarcoma and osteosarcoma) with tabular salivary ductal adenocarcinoma. A short review of the literature is also presented and the poor prognosis of these tumours, in spite of complete surgical removal and additional radiation therapy and chemotherapy, is discussed.