Ductal Carcinoma In Situ (DCIS):
Incidence, Prognosis, and Diagnostic Aspects of Mammography,
Galactography, and Needle Biopsies
Gunilla Svane
114
Summary. Ductal carcinoma in situ (DCIS) is mostly diagnosed by mammography.
The incidence is between 1% and 5% in countries without widespread use of mam- mography, but the incidence in mammography screening programs is between 8%
and 25%. However, DCIS can also be diagnosed by galactography in patients with nipple discharge, by ultrasound, and sometimes also by MRI. These methods can tell precisely how big the cancer is and exactly where in the breast. However, to morpho- logically verify a suspicion of malignancy from any of these imaging methods, needle biopsy can be performed. By using needle biopsy, surgery can be planned more accu- rately as a curative measure instead of as a diagnostic biopsy. Fine-needle biopsy with thin needles for cytological diagnosis can be used successfully, especially in DCIS of the comedo type, but this technique is more operator dependent than core-needle biopsy and vacuum-assisted biopsy techniques where small pieces of tissue are sampled for histopathological analyses and diagnosis. There are no real complications for all these techniques. Patients diagnosed with DCIS have an excellent prognosis to survive without any local recurrences and general metastases.
Key words. Breast cancer, Ductal carcinoma in situ, Mammography, Galactography, Needle biopsy
Breast cancer is the most common malignancy in women in many countries.
In Europe alone, more than 300 000 cases were estimated in 1995 and approximately 124 000 women died of breast cancer [1]. However, there are geographical differences in the risk of developing breast cancer. High rates of incidence are observed, espe- cially in Western Europe and the United States, while the incidence is low in, for example, Japan. Family history of breast cancer might be important also for the devel- opment of cancer in situ. Claus and coworkers found that patients with ductal carci- noma in situ (DCIS) were 2.4 times more likely than controls to have both mother and sister previously diagnosed with breast cancer. Their risk of developing DCIS before the age of 50 was 2.1 fold the risk of controls [2]. However, the prognosis of breast cancer is improving in some countries, most probably as a consequence of earlier
Department of Diagnostic Radiology, Karolinska Hospital, S-171 76 Stockholm, Sweden
detection by mammography and thereby earlier surgical treatment, but also because of improvement of endocrine therapy and chemotherapy of advanced tumors. Mor- tality in breast cancer has been reduced, especially where mammography screening programs are ongoing. In these programs, most of the tumors are stage I, without lymph node metastases and about 50% have a diameter of less than 1 cm. The prog- nosis for noninvasive breast cancers and of invasive cancers with a diameter of only 1 cm or less is excellent [3, 4]. Mokbel found the specific breast cancer mortality to be 0.59% for patients diagnosed with DCIS only. He found that local recurrences of DCIS are rare, only 1.4%, which can be reduced even further by radiotherapy [4].
Cancer in situ was first described 70 years ago as a tumor where the cells show marked atypia like malignant cells but the cells are not infiltrating into surrounding tissue. There are two different types of in situ cancer, the ductal type and the lobular type. The lobular type (LCIS) is usually not detected preoperatively by clinical ex- amination or by any of our breast imaging methods. It is usually detected under the microscope when a surgical specimen of another tumor is examined.
The incidence of DCIS without any invasive tumor is very low in clinical practice, usually 1% to 3%. Rarely, DCIS presents as a palpable lump found by the patient herself or by a physician. However, in mammography screening programs DCIS is more common, usually between 8% and 25%. DCIS are mainly detected by mam- mography, where the tumor usually presents as calcifications but sometimes also as parenchymal distortion. Only rarely does DCIS show an increased density. Due to technical improvement of ultrasound equipment and more trained physicians per- forming ultrasound examinations, DCIS can nowadays be diagnosed by ultrasound as well. Also, magnetic resonance imaging (MRI) can show DCIS.
Since three to four decades ago, patients presenting with discharge from the nipple can be examined by galactography where contrast is injected into the duct from which the discharge is coming. The common finding is a lobulated filling defect correspond- ing to a papilloma, but irregular contrast filling defects along the ductal walls can rep- resent epithelial proliferations that sometimes correspond to DCIS. The sensitivity of galactography for any neoplasm, according to Dinkel and coworkers, is 94% and the specificity is 55% [5]. They found sensitivity and specificity for malignancy to be slightly lower, 83% and 41%, respectively. The color of the discharge is an important factor. Hou et al. reported that cancer was found in 26.8% of patients with bloody dis- charge and in 13% of patients with serous discharge. No patients with discharge of other types had a malignant tumor [6]. They also found that cancer in 75.7% pre- sented as irregular contrast filling defects whereas benign lesions showed dilatation of the ducts in 71.7% and lobular smooth contrast filling defects in 79.6%. DCIS can also be detected by fiber ductoscopy (FDS), which is used in clinical practice, espe- cially in Japan [7]. FDS is a very sophisticated and impressive method by which the intraductal changes can be visually observed [8]. However, the most common way to detect DCIS is still by mammography, where the tumor mostly presents as clustered or scattered microcalcifications only. A meticulous evaluation of the calcifications from magnification views is necessary to correctly handle the patient and to decide if further investigations are necessary.
A morphological evaluation of the lesions to confirm the mammographic evalua- tion can be done by needle biopsy [8]. A benign morphological report can confirm the mammographic evaluation of a benign lesion and surgery can be avoided. When
morphology shows malignancy, surgery can be performed as a curative measure at once instead of as a surgical diagnostic biopsy. Because DCIS rarely presents as a pal- pable lump or a retraction of the skin, needle biopsy can rarely be performed by free- hand. Two-dimensional localization methods that can be used to sample cells or tissue from invasive cancers are usually not precise enough to sample cells or tissue from noninvasive tumors, especially because an increase in density is almost never found;
this means that very little or no difference in resistance of the tumor compared to sur- rounding tissue can be felt through the needle. A three-dimensional localization method is necessary, especially as many of the DCIS are only a couple of millimeters in diameter and sometimes several foci of only 1 to 2 mm are separated by normal ducts. The three-dimensional stereotaxic technique has been used since 1976 in clini- cal practice for needle biopsies of both invasive and in situ tumors; the precision has been ±1 mm from the very beginning [9, 10].
Ultrasound guidance can be used in all tumors detected by ultrasound. The next step is to choose a needle. Both fine needles for cytological diagnosis and bigger needles for histopathology can be used. Fine-needle cytology is more demanding and very much dependent on the skill of the operators. Both the doctor performing the sampling of the cells and the cytologist reading the smears have to be well trained and experienced. An abundant amount of cells is necessary for a correct evaluation.
Some DCIS show only little cell atypia and can be difficult to diagnose, whereas DCIS of the comedo type usually are easy to sample cells from and also to analyze correctly because the cells show pronounced atypia. Core-needle biopsy and vacuum-assisted biopsy are less operator dependent [11]. A fragment of tissue might be easier for the pathologist to analyze than cells only. However, it might sometimes be easier to sample representative material from the exact area by a thin needle than by a big needle, es- pecially if the diameter of the tumor is only, 2 to 3 mm. Shortage of experienced cytologists is a problem in many places, and this is one important reason not to use fine-needle biopsy.
In general, fine-needle biopsy of DCIS is reported to result in a higher percent- age of false-negative reports than core biopsy or vacuum-assisted biopsy [12, 13].
However, there are false-negative reports also when these needles are used [14]. Espe- cially, a preoperative morphological diagnosis of atypical ductal hyperplasia (ADH) might turn out to be a false-negative report [15–17]. A postoperative diagnosis of DCIS or invasive ductal cancer can be found in some of the lesions diagnosed pre- operatively as ADH. The false-negative reports for fine-needle biopsy in DCIS is generally 15% to 30%, but there are reports of 60% false-negative reports. The false- negative figures for core-needle biopsy vary from 10% to 40% depending upon the size of the needle and the number of passes. Vacuum-assisted biopsy is more precise according to some authors, but false-negative reports in 5% to 25% have been reported. A cytologist rarely can tell if the tumor is invasive. Also, tissue from core- needle biopsy and vacuum-assisted biopsy showing DCIS might turn out to cor- respond to an invasive cancer when the surgical specimen is examined [18–20].
However, mammography and/or ultrasound can be used to determine if the tumor is invasive. The tumor is most probably invasive when the mammograms show an increased density and/or spiculae and not only calcifications.
A preoperative evaluation of the mammograms, the galactograms, and/or the ultra- sound examination performed by physicians experienced in reading the images is
essential for a correct handling of the patient even if a needle biopsy is performed.
The report from the cytologist/pathologist should always be evaluated together with our breast imaging methods in order not to miss a cancer and thereby delay diagno- sis of a DCIS, which then might grow to become an invasive tumor. There are almost no real complications after needle biopsy. However, there are some reports of seeding of tumor cells in the needle track after large-needle biopsy [21–23].
Local recurrences of DCIS are rare when mastectomy has been performed. Spiegel and co-workers reported no local recurrence after a mean follow-up period of 9.8 years in 44 patients with DCIS alone who were operated upon with skin-sparing mas- tectomy and immediate breast reconstruction [24]. Also, breast conservative surgery with postoperative radiation therapy seems to be sufficient in most of the cases.
However, a radical excision is important. Aref et al. showed residual microcalcifica- tions in 16 postlumpectomy mammograms in 90 patients with DCIS [25]. Despite peroperative radiography of the excised specimen, a postoperative mammography examination might be necessary to verify that all calcifications have been excised, especially if the calcifications are scattered and not in a small cluster.
References
1. Bray F, Sankila R, Ferlay J, et al (2002) Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer 39:99
2. Claus EB, Stowe M, Carter D (2003) Family history of breast and ovarian cancer and the risk of breast cancer in situ. Cancer Res Treat 78(1):7–15
3. Tabár L, Dean P, Kaufman CS, et al (2000) A new era in the diagnosis of breast cancer.
Surg Oncol Clin N Am 9(2):233
4. Mokbel K (2003) Towards optimal management of DCIS of the breast. Eur J Surg Oncol 29(2):191–197
5. Dinkel HP, Gassel AM, Muller T, et al (2001) Galactography and exfoliative cytology in women with abnormal nipple discharge. Obstct Gynecol 784:625–629
6. Hou MF, Huang TJ, Liu GC (2001) The diagnostic value of galactography in patients with nipple discharge. Clin Imaging 25(2):75–81
7. Okazaki A, Hirata K, Okazaki M, et al (1999) Nipple discharge disorders: current man- agement and the role of fiber-ductoscopy. Eur Radiol 9:583–590
8. Martin HE, Ellis EB (1930) Biopsy by needle puncture and aspiration. Ann Surg 92:
169–181
9. Nordenström B, Rydén H, Svane G (1981) Breast. In: Zornoza J (ed) Percutaneous needle biopsy. Williams & Wilkins, Baltimore, p 43
10. Svane G, Silfverswärd C (1983) Stereotaxic needle biopsy of non-palpable breast lesions. Cytologic and histopathologic findings. Acta Radiol Diagn 24 (4):283 11. Elvin A, Andersson T, Jaremko G, et al (1994) Significance of operator experience in
diagnostic accuracy of biopsy gun biopsies. Eur Radiol 4:430
12. Lifrange E, Kridelka F, Colin C (1997) Stereotaxic needle core biopsy and fine needle aspiration biopsy in the diagnosis of non-palpable breast lesions: controversies and future prospects. Eur J Radiol 24:39
13. Leifland K, Lundquist H, Lagerstedt U, et al (2003) Comparison of preoperative simul- taneous fine needle aspiration biopsy and core needle biopsy in ductal carcinoma in situ of the breast. Acta Radiol Diagn 44:213–217
14. Liberman L, la Trenta LR, Van Zee KJ, et al (1997) Stereotaxic core biopsy of calcifica- tions highly suggestive of malignancy. Radiology 203:673
15. Cangiarella J, Waisman J, Symmers WF, et al (2001) Mammotome core biopsy for mammary microcalcification: analysis of 160 biopsies from 142 women with surgical and radiological follow up. Cancer (Phila) 119(1):173
16. Adrales G, Turk P, Wallace T, et al (2000) Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome? Am J Surg 180(4):313 17. Joshi M, Duva-Frissora A, Padmanabhan R, et al (2001) Atypical ductal hyperplasia in
stereotactic breast biopsies: enhanced accuracy of diagnosis with the mammotome.
Breast J 7(4):207
18. Renshaw AA (2002) Predicting invasion in the excision specimen from breast core needle biopsy specimens with only ductal carcinoma in situ. Arch Pathol Lab Med 126(1):39–41
19. King TA, Farr GH Jr, Cederbom GJ, et al (2001) A mass on breast imaging predicts coexisting invasive carcinoma in patients with a core biopsy diagnosis of ductal car- cinoma in situ. Am Surg 67(9):907–912
20. Wahedna Y (2001) Mammographic size of ductal carcinoma in situ does not predict the presence of an invasive focus. Eur J Cancer 37(4):459–462
21. Diaz LK,Wiley EL,Venta LA (1989) Are malignant cells displaced by large-gauge needle core biopsy of the breast? AJR (Am J Roentgenol) 173(5):1303–1313
22. Stolier A, Skinner J, Levine EA (2000) A prospective study of seeding of the skin after core biopsy of the breast. Am J Surg 180(2):104–107
23. Davies JD, Nonni A, D’Costa HF (1997) Mammary epidermoid inclusion cysts after wide-core needle biopsies. Histopathology (Oxf) 31(6):549–551
24. Speigel AJ, Butler CE (2003) Recurrence following treatment of DCIS with skin-sparing mastectomy and immediate breast reconstruction. Plast Reconstr Surg 111(2):706–711 25. Aref A, Youssef E, Washington T, et al (2000) The value of postlumpectomy mammo- gram in the management of breast cancer patients presenting with suspicious micro- calcifications. Cancer J Sci Am 6(1):11–12
