Clinicopathologic correlations and significance of clinically occult mammary lesions

Experience with 189 clinically occult, i.e., nonpalpable breast lesions is presented. The described technique of localization and excision all but guarantees removal of even the smallest radiographically suspicious findings with an inconspicuous incision and minimal breast deformity. The incidence of carcinoma encountered in these 189 biopsies is 27.5%. Axillary node metastases were present in less than 25% of the invasive nonpalpable cancers, approximately half of what might have been expected if the lesions had been discovered in the usual manner. There were no patients with axillary node metastases among those with in situ ductal or microinvasive ductal carcinomas. This implies a better prognosis and lower death rate from breast cancer in these patients. Screening programs employing mammography, designed to detect breast cancers in this pre-palpable stage, are encountered as a means of uncovering a higher proportion of such cancers at an earlier stage in their natural histories.     

On the occurrence of focal, occult in situ and invasive carcinoma in 250 mastectomy specimens

In 1982, a total of 250 breasts were removed for cancer in the surgical departments of the Oslo City Health Department, comprising 81% of all new breast cancers reported in Oslo in 1982. Invasive ductal carcinoma (68%) and invasive lobular carcinoma (12.4%) were the predominant types. Special attention was given to the presence of occult in situ or invasive carcinomas more than 1 cm from the periphery of the main carcinoma. In 24.8% of the specimens, carcinoma in situ was found in such locations, and an additional 6.9% showed a second, occult invasive carcinoma. Carcinoma in situ was equally common in invasive ductal and invasive lobular carcinoma. Occult invasive carcinoma was predominantly found in specimens with invasive lobular carcinoma. There was a significantly increased number of lymph node metastases in patients with carcinoma in situ or second, occult primary carcinoma more than 1 cm from the periphery of the main carcinoma.     

Breast cancer diagnosis and prognosis in women augmented with silicone gel-filled implants

From 1981 through 1988, 35 patients with prior augmentation mammoplasty were treated for breast carcinoma. Thirty-two patients had unilateral infiltrating carcinomas; three had noninvasive (in situ) lesions. Thirty-four of 35 (97%) lesions were palpable. One noninvasive cancer was occult, discovered mammographically in the absence of physical findings. Prebiopsy mammography was performed in 29 patients with palpable masses and failed to reveal an abnormality in 12 patients, a false-negative rate of 41%. Fifteen patients were treated with mastectomy; the remaining 20 with breast preservation. Thirty-two patients underwent axillary node dissection; 15 (47%) patients had lymph node metastases. There have been seven (20%) recurrences: one local and six metastatic. Four (11%) patients have died. The median follow-up time is 48 months. Women, previously augmented with silicone gel-filled implants, who develop breast cancer are similar in terms of nodal positivity and prognosis, to nonaugmented breast cancer patients who present with palpable masses. When compared with nonaugmented women whose cancers were found with screening mammography, augmented patients with breast cancer present with a higher percentage of invasive lesion and involved axillary lymph nodes, resulting in a poorer prognosis.     

Mammographically occult breast cancer. A pathologic and radiologic study

Fifteen mammographically occult breast cancers, 3 of which were preinvasive and 12 invasive, and 52 breast cancers, which presented only microcalcifications mammographically without an associated tumor shadow (33 preinvasive and 19 invasive), were reviewed pathologically and radiologically. This study suggests that most of the preinvasive cancers, without mammographically significant calcifications, are, and some of the invasive cancers situated in dense breasts may be, mammographically occult. The mean diameter of the five mammographically occult invasive ductal carcinomas and the five invasive lobular carcinomas was 20 mm and 50 mm, respectively. Histologic characteristics, which may explain why invasive lobular carcinomas could be occult mammographically, even in an advanced stage, include a diffuse invasive pattern and, frequently, a poor desmoplastic reaction in contrast to the invasive ductal carcinomas. The implications of mammographically occult cancers on management of symptomatic and asymptomatic patients are discussed.     

Tuberculosis of axillary lymph nodes with primary breast cancer

A rare case of tuberculosis of axillary lymph nodes occurring with primary breast cancer is presented. A 78-year-old woman with no history of pulmonary tuberculosis was admitted to our hospital to undergo examination for a lump in her right breast. The tumor was in the upper outer quadrant of the right breast. On palpation, the tumor was 1.2 cm in diameter and axillary lymph node swelling was noted. Mammography disclosed a spiculated mass and swelling and calcification of the axillary lymph nodes. Sonography showed an irregular hypoechoic mass in the right breast and lymph node swelling in the right axilla, indicating breast cancer with axillary lymph nodes metastases. Chest X-ray showed clustered calcifications in the right axilla and a granular shadow in the right upper lobe. Breast conserving therapy was carried out. Invasive papillotubular carcinoma of the right breast and granulomas with calcification of lymph nodes, compatible with tuberculosis, was diagnosed. Tubercle bacillis were detected by culture of lymph nodes. This case suggests that X-ray is useful for diagnosing lymph node tuberculosis. Lymph node tuberculosis should be suspected when lymph node swelling is noted and X-ray shows clustered calcifications in axillary lymph nodes.     

乳腺X线摄影检出的恶性微钙化在MR上的影像表现

目的:探讨乳腺X线摄影检出的恶性微钙化病变在MR上的影像表现。方法:回顾性分析乳腺X线摄影上表现为微钙化且手术病理证实为乳腺癌的80例患者资料,均行乳腺MR检查及X线引导下金属丝定位。分析其X线、MR表现及两者的关系。统计学采用卡方检验或Fisher's 精确检验。结果:共83个病灶,导管内癌45个,浸润性癌38个。X线表现:67个为单纯钙化,16个钙化伴局部密度增高;细小多形性（49个）及簇状分布（35个）是最常见的钙化形态及分布方式。MR表现:非肿块样强化57个,肿块样强化16个,未见异常强化10个。92.9%（26/28）的段样分布钙化MR上表现为段样分布强化。段样分布钙化灶在MR上以段样分布强化更常见（P=0.000）。81.3%（13/16）的肿块样强化见于簇状分布钙化。肿块样强化更多见于簇状分布的钙化灶（P=0.000）。MR上假阴性钙化灶多见于簇状分布钙化灶,但没有显著差异（P=0.061）。结论:恶性微钙化在MR上的强化类型以非肿块样强化常见,少部分表现为肿块样强化。其强化表现与钙化在X线上的分布方式有关。     

Surgery for ductal carcinoma in Situ

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.     

Survival in bilateral breast cancer

The presence of bilateral invasive breast cancer places the patient in a state of double jeopardy. At Memorial Sloan-Kettering Cancer Center, the overall 10-year recurrence rate for unilateral Stage I breast cancer was 16%, whereas the recurrence rate for simultaneous, bilateral Stage I breast carcinoma was 29%: almost twice as high. The average 10-year survival of all patients with negative axillary nodes was 57%. In this retrospective analysis of 403 patients with bilateral primary operable breast cancer treated at Memorial Sloan-Kettering Cancer Center, significant differences were noted in the disease-free survival between patients with bilateral noninvasive cancer, bilateral invasive cancer, and the combination of invasive and in situ cancers. Bilateral intraductal cancer and lobular carcinoma in situ offered an excellent prognosis. The combination of preinvasive cancer on one side and infiltrating carcinoma on the other had the next best survival. The in situ lesion, when treated by mastectomy, did not alter the patients' life expectancy from that of the general population with unilateral breast cancer, thus indicating that surgeons should strive to detect breast cancer in its preinvasive form. The 5- and 10-year relapse-free survival of patients with bilateral invasive disease, regardless of axillary nodal status and tumor size, was 60% and 51%, respectively, for patients with a bilateral presentation and 54% and 38%, respectively, for carcinomas presenting metachronously. More important in determining prognosis, however, was the number of axillary nodes involved and the level of involvement. Invasion of bilateral axillary nodes at all levels predicted a poor prognosis. Because of this shortened survival, systemic adjuvant therapy should be considered for patients with bilateral invasive disease. The most common preinvasive breast cancer was lobular carcinoma in situ and the most frequently invasive tumor was infiltrating duct cancer. Since a contralateral breast cancer at the time of definitive treatment of the first side does not always present as a mass or with positive mammography, a random biopsy of the second breast is recommended. This should be done in the upper, outer quadrant and should include the subareolar area. With prompt adequate treatment, it is expected that survival from bilateral breast cancer should improve.     

Changes in Incidence of in situ and Invasive Breast Cancer by Histology Type following Mammography Screening

Objective: To investigate secular trends and correlates of incidence of breast cancer by histology type following ‍the introduction of population-based mammography screening. Methods: Analysis of age-standardised incidence ‍rates for 1,423 in situ and 16,157 invasive carcinomas recorded on the South Australian population-based cancer ‍registry for the 1985-2004 diagnostic period. Multiple logistic regression was undertaken to compare sociodemographic ‍characteristics by histology. Progression from in situ disease was investigated using the Kaplan-Meier ‍method. Results: The incidence of in situ lesions increased approximately seven-fold over the 20-year period, compared ‍with an increase of about 40% for invasive cancers. The increase for in situ lesions was due to increases for ductal ‍carcinomas, with little change for lobular lesions. By comparison, the percentage increase in incidence for invasive ‍cancer was greater for lobular than ductal cancers. Both for in situ and invasive cancers, percentage increases were ‍greatest for the screening target age range of 50-69 years. One in 14 in situ cases was found to progress to invasive ‍cancer within seven years of diagnosis, but insufficient detail was available to determine whether the invasive cancers ‍were a progression of the in situ lesions or whether they originated separately. These invasive cancers were smaller ‍than generally applying for other invasive cancers of the female breast. Conclusions: The larger secular increases in ‍incidence for in situ than invasive cancers would reflect the dominant role of mammography in the detection of ‍ductal carcinoma in situ. The lack of an increase for lobular in situ lesions may have resulted from their poorer ‍radiological visibility. The greater percentage increase for lobular than ductal invasive lesions may have been due to ‍an increase in imaging sensitivity for these lesions, plus real increases in incidence. The smaller sizes of invasive ‍cancers found in women with a prior in situ diagnosis may have resulted from more intensive medical surveillance, ‍although the possibility of biological differences cannot be discounted.     

触诊阴性乳腺病灶术中冰冻诊断的可行性分析

 目的 探讨触诊阴性乳腺病灶活检术中冰冻诊断的准确性与可行性。方法 由钼靶发现的触诊阴性乳腺病灶158例，采用金属线定位技术切除活检，术中进行冰冻切片与诊断，以石蜡组织学诊断为准，评价冰冻诊断的准确性。结果 158例标本中，病理巨检时仅80例（50．6％）发现肉眼可见的异常病灶，平均长径1．2cm。石蜡组织学诊断乳腺浸润癌15例，微小浸润导管癌15例，原位癌12例，导管上皮不典型增生5例，占29．7%（47／158）。术中冰冻对乳腺浸润癌诊断的准确率为93．3％，对微小浸润癌、原位癌、导管上皮不典型增生诊断的准确率分别为60％、58．3％与60％，误诊均为假阴性与低估诊断，无假阳性与过度诊断，原因主要为切片误差与解释错误。结论 冰冻切片对浸润性乳腺癌诊断的准确率高，可用于指导触诊阴性乳腺病灶活检术中手术方案的选择，而对微小浸润癌、原位癌及导管上皮不典型增生常出现假阴性与低估诊断，应待石蜡组织学诊断后再决定手术方案。     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.      

Hooked-wire-directed breast biopsy and overpenetrated mammography

Six hundred fifty-three biopsies were performed for clinically occult, mammographically detected breast abnormalities. One hundred forty-seven cancers (22.5%) were found. Eighty-nine of those cancers (60.5%) were noninvasive. None of the in situ lesions had involved axillary lymph nodes. Of the 58 invasive cancers, only six (10.3%) had metastases to axillary nodes. Fifty-four patients (36.7%) were treated by mastectomy while 93 patients (63.3%) were treated conservatively, 20 by biopsy only, and 73 by lumpectomy, axillary node dissection, and radiation therapy. Only four patients (0.7%) had significant complications.     

Clinical management of minimal breast cancer

Minimal breast cancer includes three different entities: lobular carcinoma in situ, noninfiltrating intraductal carcinoma, and invasive carcinoma less than 0.5 cm. The common feature is their small dimensions and the fact that they are often clinically occult. For lobular carcinoma in situ the risk of developing an invasive carcinoma varies from seven to nine times compared with the general population and a careful follow-up of the patients with frequent mammograms is therefore suggested. Intraductal noninfiltrating carcinoma should be locally treated as an invasive carcinoma of small size, and therefore an extensive mammary resection like the quadrantectomy, plus radiotherapy is the recommended form of treatment, while the axillary dissection may be avoided. Finally, small invasive carcinomas should be treated with conservative procedures, including a total axillary dissection.     

Occult Breast Cancers Manifesting as Axillary Lymph Node Metastasis in Men: A Two-Case Report

Occult breast cancer is a type of breast cancer without any symptoms on the breasts or any abnormalities upon radiologic examination such as mammography. In males, there are few cases of breast cancer, the rate of diagnosis of occult breast cancer is very low, and little is known about this disease. We experienced two cases of occult breast cancers manifesting as axillary lymph node metastasis in men. They had a palpable lesion on axillary area several years ago and had not seen a doctor about it. As such there was no abnormality on evaluations for cancer except for axillary lymph node showing signs of carcinoma (primary or metastatic) on biopsy and estrogen receptor-positive and progesterone receptor-positive on immunohistochemistry. The patients were diagnosed with occult breast cancer, and treatments were performed. Herein, we report the rare cases of occult breast cancers in men.     

Ultrasound demonstration of mammographically detected microcalcifications in patients with ductal carcinoma<Emphasis Type="Italic">in situ</Emphasis> of the breast

BACKGROUND: Breast microcalcifications are difficult to depict by ultrasound (US). However, recent advances in US equipment and the refinement of breast imaging techniques have improved the detection and characterization of small breast lesions. The present study attempts to determine whether US examination is able to demonstrate nonpalpable breast lesions associated with mammographically detected microcalcifications without mass density or distortion, and to evaluate the clinical reliability of US-guided procedures, especially in cases of ductal carcinoma in situ(DCIS)of the breast. METHODS: The subjects consisted of 73 patients with breast cancer diagnosed preoperatively as DCIS by stereotactic core needle biopsies, all of whom had microcalcifications without other abnormalities on mammography. The radiological appearance and size of the clustered microcalcifications were evaluated. US examinations were performed preoperatively, and the detection rates were assessed. Sonographically detected lesions underwent US-guided wire localization followed by surgical excision. RESULTS: The lesions associated with microcalcifications were identified sonographically in 54 of 73 cases (74%), and the pathological examination revealed breast cancer in all of the corresponding specimens. Lesions with linear-branching shape, segmental-linear distribution and category-5 calcifications on mammography had a high level of visibility on US. The US visible cases had a larger size of calcified area on mammography when compared with US invisible cases. Pathologically, the lesions were more frequently seen on US in cases with minimally invasive cancer or with comedo type DCIS. CONCLUSIONS: US examination is an effective method for identifying and localizing breast microcalcifications, and can be used as an alternative to stereotactic localization in selected patients with early breast cancer.     

Sentinel lymph node biopsy and management of the axilla in ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) of the breast historically has been a disease detected by physical examination, diagnosed by open surgical biopsy, and treated by mastectomy and axillary dissection. It is now increasingly detected by screening mammography, diagnosed by needle core biopsy, and treated by lumpectomy, with axillary dissection having been abandoned and sentinel node biopsy being used in axillary staging. However, outcomes related to sentinel node biopsy in DCIS have not been validated in well-controlled clinical trials. Current guideline recommendations are to use sentinel node biopsy when needle core biopsy is highly suspicious for invasive cancer or where there is a high-risk DCIS when lumpectomy identifies invasive breast cancer with the DCIS, or when mastectomy is performed for extensive DCIS. Routine use of sentinel node biopsy for DCIS is not supported.     

数字化X线摄影在触诊阴性乳癌中的诊断价值

目的探讨数字化乳腺X线摄影对隐性乳癌的诊断价值。方法回顾性分析我院2004年2月-2006年12月门诊体检中遇到的32例未触及肿块乳癌。术前均行金属丝定位,并经病理证实。结果X线呈现单纯钙化16例,其中癌前病变3例,导管原位癌6例,浸润性导管癌7例;微结节或致密影伴钙化5例,其中癌前病变1例,导管原位癌2例,浸润性导管癌2例;呈现不对称性致密影5例,1例为小叶原位癌,4例为浸润性导管癌;微结节伴浅分叶或毛刺4例,其中1例为导管原位癌,3例为浸润性导管癌;结构紊乱2例,均为浸润性导管癌。结论数字化乳腺X线摄影对诊断未触及肿块的触诊阴性乳癌、提高患者生存率、降低病死率、以及开展保乳手术具有重大价值。     

Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti‐NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.     

The occurrence of interval cancers in the Nijmegen screening programme

Since January 1975 a population-based screening programme for the early detection of breast cancer has been carried out in the city of Nijmegen. During five interscreening periods of 2 years each a total of 158 so-called interval cancers were diagnosed. Careful revision of all screening and diagnostic mammograms was executed. Of all interval cancers 26% were 'missed' at the previous screening examination (due to technical or observer error), 16% were radiographically occult at the time of diagnosis and 58% were 'true' interval cancers. Interval cancers were regarded as 'true' when an obvious lesion was observed on the diagnostic mammogram while no suspect signs were seen on the previous screening mammogram. The prevalence of 'missed' cancers did not decline in the course of the screening programme. Radiographically occult tumours were localised, mostly in Wolfe's P2/DY breast parenchyma (83%), 33% were lobular invasive and 25% ductal non-invasive. 'True' interval cancer cases (58%) showed the same overall survival as control breast cancer patients, diagnosed in a non-screening situation. Shortening the screening interval would reduce interval cancer rates and probably further decrease breast cancer mortality in a screened population. However, from the present series of interval cancers 63% would not have been prevented by an annual screening examination. As regards women under age 50 annual screening would still leave 66% of all interval cancers in this age group undetected. Probably more benefit will be gained by searching for new imaging techniques to reduce numbers of 'missed' cancers and to detect lobular invasive and ductal non-invasive cancers in dense breast parenchyma.     

Surveillance of women at increased risk of breast cancer using mammography and clinical breast examination: further evidence of benefit

Women with a significant family history of breast cancer are generally offered early surveillance by mammography and often clinical breast examination (CBE). The evidence base for surveillance has been questioned. We reviewed its effectiveness in terms of tumour size, lymph node status and survival in 7,475 women seen over a 22-year period in the Manchester Family History Clinic. We diagnosed 139 invasive and 26 in situ breast cancers. Seventy-six percent of the invasive cancers were screen detected, 65% node negative and 71% <2 cm in diameter at diagnosis. Twenty-one tumours were BRCA1 positive and were significantly more likely to be grade 3, ER/PR negative (p < 0.0001) and have a poorer survival. CBE contributed to 30% of cancer diagnoses and was responsible for discovery of nine mammographically occult tumours. The cost per quality life year was estimated at ￡13,080 for tumours detected by CBE and not by mammography. We conclude that screening by annual mammography and CBE between age 35-50 years and 18 monthly from 50 to 60 years may diagnose breast cancer in a less advanced state in terms of size and node status compared with symptomatic cancers and, apart from BRCA1 carriers, is likely to contribute to improved long-term outcome compared with no surveillance.