7.3. Breast Cancer: Correlations Between Imaging and Morphological Details. Spiculated Densities. Introduction. Chapter.

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1 Chapter Breast Cancer: Correlations Between Imaging and Morphological Details 7.3 Edward Azavedo Contents Introduction Spiculated Densities Developing Density Medullary and Mucinous Carcinomas Radiating Lesions Without a Central Density Topographic and Other Characteristics of Breast Cancers. 787 References Introduction Breast cancer is the most common malignancy that can affect a woman during her lifetime. In Sweden it comprises 27% of all malignancies in women. During the last 30 years, the detection of breast cancers has shifted from palpable tumours in symptomatic women to impalpable tumours in asymptomatic women. This is mainly the result of the widespread use of imaging modalities, particularly mammography in mass screening programs [1]. Mammography is today the method of choice to screen healthy asymptomatic women for breast cancer and the immediate adjunct method is ultrasound technology. While mammography does detect small impalpable breast cancers, it also has the ability to detect abnormalities representing minor non-malignant but pathological changes. In this respect, the interpretation of imaging findings with correlation to morphological changes is mandatory to minimize harm and worries [2]. There are several typical imaging findings that can be correlated with morphological changes representing malignancies, and this knowledge is essential for further specific diagnostic interventions. Stereotaxic and ultrasound-guided interventions can provide us cells or tissue material for morphological assessment and these reports have to be consistent with the imaging diagnosis [3, 4]. Spiculated Densities The most common type of screening-detected breast cancer is the spiculated lesion, with or without microcalcifications. This type of lesions corresponds to 61% of all screening-detected breast cancers in our screening experience [5]. Some of the typical imaging characteristics of cancers appearing as spiculated densities are: a. Focal density that is higher than surrounding tissue b. Spicula that are short, fine and concentric c. Spicula that are seen at the border zone almost around the entire density d. Spicula that do not cross the density under consideration Details such as the increase in density correspond to an increased number of cells as compared to the surrounding tissue and the spicula correspond to the outward growth of a malignancy from the centre of the density. These details are shown in Figs Ultrasound examinations of these tumours will show a solid lesion where some of the features such as echogenicity (hypoechoic or anechoic), contours (irregular margins), form (depth greater than width) are typical Fig. 1. Sketch of a spiculated density that shows concentric spicula and a sketch showing two different sizes of one and the same tumour

2 786 Edward Azavedo Fig. 2. Spiculated densities in a case of invasive carcinoma that shows fine, short and concentric spicula Fig. 4. Histopathology of an invasive carcinoma, a spiculated density on a mammogram, showing the outward-growing cancer cells that represent the fine and short spicula for malignant lesions [6]. This appearance on sonography is rather typical for both spiculated densities and other kinds of invasive malignancies, even though some malignant tumours may show quite regular margins to the surrounding tissue. Some indirect signs of malignancy often seen in conjunction with solid malignant lesions are pseudoradiolucency around a tumour and effects on the skin near a tumour. The pseudoradiolucency, also called peritumoral corona, is a radiolucent zone around a tumour, and this is usually seen when fat surrounds a tumour (Fig. 3). This peritumoral corona is different and should be distinguished from the halo sign around solid lesions with sharp margins that represent a benign lesion [7, 8]. Effects on the skin usually comprise skin thickening with folded and/or retracted skin near a malignant tumour, indicating contraction of tissue surrounding a tumour. Developing Density Fig. 3. Peritumoral corona (pseudoradiolucency) A developing density in a radiolucent area or an increasing density in an already dense background is another common phenomenon that should worry a breast imager. Transition from a radiolucent to a radiopaque area or a focal increase in density in an existing dense area should mean an increased number of cells until the contrary is proven. Ultrasound can rather easily differentiate a cystic from a non-cystic increase in density. A developing non-cystic density warrants action to find an explanation for the increase in density that in many a case may be a malignancy, even if benign changes such as fibrosing adenosis could be the correct diagnosis. Even if a developing non-cystic density lacks spicula, it is mandatory to assess the finding morphologically either with cytology or histology. When using only cytology, one must make sure that the needle positioning is

3 Chapter 7.3 Breast Cancer: Correlations Between Imaging and Morphological Details 787 right and that the material obtained through fine needle aspiration (FNA) is adequate enough to make a cytological diagnosis. Lobular carcinomas that grow diffusely in a dense area may pose a challenge to a cytologist, since the number of epithelial cells obtained could be minimal due to the abundant fibrous background containing fibroblasts, collagen, etc. In addition, low-grade lobular carcinomas are often of the small cell type with very little cell atypia. Histological assessment with core biopsies could be a good complement or alternative in such situations. Rather typical lobular carcinomas are shown in Figs. 5 and 6. Medullary and Mucinous Carcinomas Medullary and mucinous carcinomas can show mixed features but appear as densities. Medullary carcinomas occur in less than 5% of all cases but are more common in younger women where the frequency can be up to 11% in women younger than 35 years of age [9]. On mammography they show up as round or oval uncalcified lesions, often with lobulated margins and homogeneous density. Mucinous carcinomas comprise about 4% of all breast cancers and are often seen in the elderly patients [10, 11]. Clinically, they could be soft and illdefined but mammographically they are usually seen as rather well-defined densities. Radiating Lesions Without a Central Density Fig. 5. A developing density in the upper outer quadrant representing a lobular carcinoma In asymptomatic women, one can sometimes find radiating lesions that do not show a central density. These lesions can be very obvious in certain projections, while they may look different in other views. They also have radiating structures that are thicker and longer than the fine spicula in a spiculated density. Moreover, the thick and long radiating structures could be parallel, sometimes 2 3 cm long, and may have fatty tissue between them.although these lesions might look like an invasive carcinoma at first sight, they are not palpable even when the size of the whole area is as big as 2 4 cm (Figs. 7, 8). These lesions, sometimes called black stars by some authors, usually represent a non-malignant pathological lesion that is called a radial scar. In our screening experience, the frequency of these lesions was 0.06%, but some authors report a much higher frequency [12]. The generally accepted management of these lesions is surgical excision, because even if the lesion is non-malignant in itself, there are reports that there could be a carcinoma associated with these lesions. Radial scars have different names and are now generally considered as a variant of sclerosing adenosis [13]. They usually lack secondary signs involving the skin such as skin thickening and skin retraction. Topographic and Other Characteristics of Breast Cancers Fig. 6. Histopathology of a lobular carcinoma According to the literature and our own experience, we find that the majority (50%) of breast cancers occur in the upper outer quadrant, approximately 25% in central

4 788 Edward Azavedo Fig. 7. A radiating lesion (stellate lesion) representing a radial scar. Note the thick and long spicula as compared to the fine spicula around a carcinoma Fig. 8.Histopathology of a radial scar showing thick fibrous strands areas around the nipple and around 5% in the lower inner quadrant [14, 15]. The more irregular the margins of a density are, the more suspicious it is of malignancy. The same is true the more lobulated a density is. The intensity of a density usually appears too high for its size when the density represents a malignancy. The size of a lesion is crucial for correct clinical staging, which in turn is the basis for adequate management. In this respect, there could be quite widespread discrepancies between sizes as evaluated on imaging modalities and sizes recorded in clinical examinations and by pathologists. In general, the size of a lesion is not enough to differentiate a lesion between benign and malignant. Comparison between mammographic and ultrasound sizes with clinical examination could show differences. If and when there is a desmoplastic reaction around a tumour, then the clinical estimate of the size of that tumour could be bigger than the mammographic size. This is also true when a tumour is situated rather centrally because the surround tissue up to the skin on both sides of the tumour will probably make it feel bigger than its actual size in the breast. We can sometimes also see differences in tumour size as seen on a mammogram and ultrasound. In some cases a desmoplastic reaction may increase the mammographic size as compared to size on an ultrasound image, but it could also be the contrary when ultrasound can show diffuse infiltration around a mass, especially in dense breasts. The size of a tumour as measured on a surgical specimen will be the final figure that will form the basis for classification and management of a case. In an elongated or an oval tumour, the recorded size of the tumour on a surgical specimen could vary depending upon how the tumour was cut, and this may be discriminatory as compared to imaging modalities (Fig. 1). In many a case microscopic examination will reveal an extensive intraductal component that cannot always be evaluated on imaging modalities, and therefore the ultimate tumour size in these cases will be bigger on surgical specimens than the imaging modalities [16]. In general malignant disease increases with age and this is true even for breast cancers. Therefore even welldefined circumscribed densities should be considered as potentially malignant in postmenopausal women. Recent trends with increasing use of HRT in peri- and postmenopausal women can be a challenge to a breast imager, who may find focal increases in density secondary to the use of HRT [17]. This demands careful analysis of every single new density that is seen on mammograms of women using HRT. Recent advances in studies regarding neoangiogenesis have shown that malignant tumours do need increased vascularization to feed growth. Histopathology can show increased vascularity with direct microscopy, and recent developments in immunohistopathology have shown that angiogenesis is quite a common factor seen and associated with malignancy. Some of these early signs can be seen with our imaging modalities that can pick-up neoangiogenesis [18]. In conclusion, breast imagers should have a regular multidisciplinary contact with surgeons, oncologists and especially pathologists for a better understanding and characterization of breast tumours.

5 Chapter 7.3 Breast Cancer: Correlations Between Imaging and Morphological Details 789 References 1. Tabar L,Vitak B, Chen HH, Duffy SW,Yen MF, Chiang CF, Krusemo UB, Tot T, Smith RA (2000) The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 38 : Tot T, Tabar L, Dean PB (2000) The pressing need for better histologic-mammographic correlation of too many variations in normal breast anatomy. Virchows Arch 437 : Azavedo E, Svane G and Ringertz H (1991) The role of the radiologist in screening for non-palpable breast tumors in Sweden. Invest Radiol 26 : Azavedo E, Svane G and Auer G (1989) Stereotactic fine needle biopsy in 2594 mammographically detected non-palpable lesions. Lancet 1 : Azavedo E, Svane G (1991) Radiologic aspects of breast cancers detected through a breast cancer screening program. Eur J Radiol 13 : Stavros AT, Thickmann D, Rapp CL et al (1995) Solid breast nodules: use of sonography to determine between benign and malignant nodules. Radiology 196 : Wylie E (1993) Malignant disease. In: Tucker AK (ed) Text book of mammography. Churchill Livingstone, New York, pp Gravelle H (1980) Mammography. In: Sutton D (ed) A textbook of radiology and imaging. Churchill Livingstone, New York, pp Meyer JE, Amin E, Lindfor KK, Lipman JC, Stomper PC, Genest D (1989) Medullary carcinoma of the breast: mammographic and ultrasonic appearances. Radiology 170 : Haagensen CD (1986) Diseases of the breast. WB Saunders, Philadelphia 11. Page DL, Anderson TJ (1987) Diagnostic histopathology of the breast. Churchill Livingstone, New York 12. Azavedo E, Svane G (1992) Radial scars detected mammographically in a breast cancer screening programme. Eur J Radiol 15 : Tucker AK (1993) Text book of mammography. Churchill Livingstone, New York 14. Zuckerman HC (1986) The role of mammography in the diagnosis of breast cancer. In: Ariel I, Cleary JB (eds) Breast cancer diagnosis and treatment. McGraw-Hill, New York 15. O Higgins N (1984) Malignant disease. In: Taylor S, Chisholm GD, O Higgins N, Shields R (eds) Surgical management. Heinemann, London, p Holland R, Hendriks JHCL, Verbeek ALM, Mravunac M, Schuurmans Stekhoven JH (1990) Extent, distribution and mammographic/histopathologic correlations of breast ductal carcinoma in situ. Lancet 335 : Lundström E, Christow A, Kersemaekers W, Svane G, Azavedo E, Söderqvist G, Mol-Arts M, Barkfeldt J, von Schoultz B (2002) Effects of Tibolone and continuous combined hormone replacement therapy on mammographic density. Am J Obstet Genecol 186 : Gamagami P (1996) Breast cancer angiogenesis. In: Atlas of mammography: New early signs in breast cancer. Blackwell Science, Oxford, pp