Known as type and type Il, there are two types of breast caleiications with distinctly different chemical compositions and characteristics (2 Table ‘on page 13). Loffera brief review of breast calcifications and then some interesting, facts about the two types. Breast cakifications were frst reported in association with breast cancer in 1951. The terms macrocalefication and microcaleification, like macro- and ‘microscopic, refer to the ability to see the caleification(9) with the naked eye or using a mieroscope. (For the purposes of this article, [will use the nonspecific term “calcifications” to include both macro- and rmicrocalcifications,) Breast calcifications are associated with palpable and nor-palpable breast lesions. At mammography, breast calcifications as ‘small as 100 microns can be visualized and may be the only radiographic abnormality detected. Although the size and number ‘of breast calcifications are important to not, itis the distribution and morphology ‘of breast caleifcations that are most indicative of malignancy. In general, irregular, pleomorphic calcifications, heterogeneous in size and measuting less than 0.5mm, are more often associated with malignancy; benign lesions tend to be associated with round or ovoid calcifications of uniform size that measure 2mm or greater Asis often the case in surgical pathology, wwe receive a specimen radiograph with a breast specimen and are asked to provide a brief remark regarding presence/absence of radiographic caleifications. Both type and type Il calcifications can be seen radiographically, however, there is a good reason why you may not have known there are two types—type Il cakcifications can be well visualized on tissue sections HE (25x) 12 Classifying Breast Calcifications stained with hematoxylin and eosin (H&E) and type Icannot. ‘Type I cakifications always contain calcium, but never phosphorus, Calcium carbonate and calcium oxalate are the ‘two main compounds classified as type Laleifications. In older references, you ‘may come across the term weddellite to describe the composition of type Tealeifications; this isa term used specifically for calcium oxalate dihydrate. ‘Type I calcifications typically have a crystalline, polyhedral shape, so are commonly referred to as crystals rather than calcifications. As previously noted, type calcifications stain poorly with H&E, but, with careful study, the calcifications can usually be picked out as colorless, well-defined, three-cimensional crystals (Images 1a and 1b). Under polarized light, these strongly birefringent caleifications are vibrantly apparent (Image 2) ‘The formation of type calcifications is less certain than type Il calcifications, Oxalate itself “isan end product of ‘metabolism and has no known metabolic value in humans” (3). Tornos et al identified type I calcifications within benign, dilated ducts, which suggests formation of oxalate crystals from breast secretions. It was originally postulated. that type I calcifications ofthe breast were ‘not found in cases of malignancy, but that has been disproved. While type I crystals may be encountered in cases of breast «cancer, the crystal themselves are not seen in direct association with the malignant lesion(s). ‘Type Il breast califications, conversely, are commonly intimately associated with both in situ and invasive breast cancer. In fact, type Il califcations often “target the location of the most important abnormality within the breast” on mammography (7). Type Il calcifications are always composed of calcium and phosphorus (predominantly calcium phosphates), with Image 4--Type Il calcifications Polarizing lens (25x) Image 1a—Type | calcifications HAE (10x) Image 2--Type | calcifications Polarizing lens (25x) ut iy Image 3: Type ll caleifications HAE (10x) Continued on next page. .300-532-AAPAhydroxyapatite its most characteristic form @). Type I ealications typically have an amorphous or spherical shape, and some may resemble psammoma bodies. These calcifications result from cellular degradation and necrosis, 0 are coften found within proliferative breast lesions, including cancer. Most type I calcifications ae identified within ducts, but may also be situated within lobules. Type ll calcifications are strongly basophilic when stained with H&E (Gmages 3a and 3b), but are not birehringent ‘under polarized light (Image 4). Calcium oxalate has @ unique staining potter (see Table); when special stains for calcium (von Kossa and lizerin ed at pH 42) are performed, calcium carbonate (type) and calcium phosphate (typeI) stain positively, but calcium oxalate does not stain, Variable staining of calcium oxalate is seen with alizatin xed stain at 1pH170, while both calcium carbonate and Calcium phosphate slain positively. Silver nitrate /rubeanic acid stain with 5% acetic acid pretreatment is fairly specific for caleium oxalate; the acetic acid dissolves calcium phosphite and caleium carbonate, ‘0 those two calcium compounds do not stain @). However, without 5% acetic acid pretreatment, all beast calcifications stain positively with silver nitrate/ rubeanic acid, In summary, type [ and type Il breast calcifications are both identified at mammography. Both calcification types may be identified in malignant breast cases, however, unlike type Il calcifications, type I caleifications have yet to be identified as part ofthe malignant lesion itself. When looking to correlate radiographic celeifcations on H&E tissue sections, only type I calcifications will be readily apparent, but only type I breast calcifications are birefringent uncler polarized light. Ifyou geta call for gross recut on a breast case where calcifeations are not identified microscopically, ask if the slides were examined with a polarizing Tens—you might save yourself (and your pathologist) some work! Author's note: Thank you to PACI Drs. Jones, Beckmann, and Gao for their kind ‘assistance in the preparation of this article, Acute Ad Petestnent PROPERTY Teed Tel ype ‘Catan Pesan IDENTIFIED AT Ye Yer MAMMOGRAPI? SHAPE Pape acne cya Shea arphom nay Damn ‘APPEARANCE: iekingom Tobin olardiog Len APPEARANCE: Coioress—wetedcpratine Bwophiie Hae Sts APFEARANCT oer ne Taek Bist ‘Yon Kos Stn at p42 APPEARANCE | Dakcbownortiaek | — Doessoraain Docs oi saia ‘iver NratRubeaic ‘Ac San ih Deskbar Das Daktrownor back Tegan ang ranged Onngesed (oeopnaeis (reise "retnge) ‘retina Weak onpaine ‘Oranasred ‘angered sarang TOCATION IN [BREAST TISSUE, ‘Wii Taino eign ata dod Tne ad, ary naar "ASSOCIATION WITH ‘BREAST CANCER incre neon May be foun ay om ae fener with cancer www pathologisteassietanss.org References: Fandos-Morera A, Prats-Esteve M, Tura-soteras JM, Traveria-Cros ‘A. Breast tumors: composition of icrocaleifcations. Radiol 1988; 168 325.827, Radi Mj. Calcium oxalate crystals in breast biopsies: an overlooked form of microcalefication associated with benign breast disease. Arch Pathol Lab Med 1989; 113: 1367-1368. ‘Tomos C, Silva E, El-Hageer A, Pritzker KPH. Calcium oxalate ‘crystals in breast biopsies: the missing microcalcifications. Am ] Surg Patho! 1990; 14(10): 961-958, Surratt JT; Monsees BS, Mazouhian G. Calcium oxalate microcalcifications inthe breast. Ratio! 1994; 181: 141-142. Frouge C, Meunier M, Guenebratiere J-M, Gilles R, Vanel D, Contesso G, Di Paola R, Biery ‘M. Polyhedral microcaleifcations at mammography: histology correlation with calcium oxalate, Ratiol 1993; 186: 681-684, Grimes MM, Karageorge LS, Hogge JP. Does exhaustive search for microcaleifications improve diagnostic yield in stereotactic core noodle breast biopsies? Mod Pathol ‘2001; 14(4) 350-353, Haka AS, Shafer-Peltior KE, Fitzmaurice M, Crowe J, Dasari RR, Feld MS. Identifying imlcrocaleifcations in benign bay probing differences in their chemical composition using rama spectroscopy. Cancer Research 2002; (62: 5375-5380, Chrzan R, Rudnicka L, Popiela TJs, Nowak W, Podsiadto- Kleinrok B. The problems with histopathoiogical verification of breast microcaleification clusters in the stereotactic mammotome biopsy specimens, Pol J Pathol 1006; 5763): 1335. http:/ /sprojects.mmi.megill.ca/ mammography /califications3 htm. Downloacled on 8 July 2010, tp: /wwwchistosearch, com/histonet/Jul07A/ Re HistonetYasuesSilverNiA. him Downloacled on 8 July 2010. hutp:/ /www:iheworld.com/_ protocols/ special. stains/slizarin_ red_shtm. Downloaded on 8 July 2010. 18