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MULTICENTRICITY OF BREAST CANCER. RESULTS OF A STUDY USING SHEET PLASTINATION OF MASTECTOMY SPECIMENS

Axel Müller, Andreas Guhr, Wolfgang Leucht (Frauenklinik) Gunther von Hagens (Anatomisches Institut)

University of Heidelberg, 6900 Heidelberg 1, West Germany

INTRODUCTION These questions may only be answered after complete histological Carcinomas of the female breast examination of breasts from total are judged to be mostly multicentric mastectomy patients suited for BCTh. (Fisher et al., 1975; Gallager and Martin, 1969; Morgenstern et al., Guhr and co-workers (1987) 1975) and only total breast removal described sheet plastination as the was recommended until about 1960. best method for fast, complete Since then, breast conserving therapy histological study of mastectomy (BCTh), i.e. surgical excision of the specimens. In the present study tumor in combination with radiotherapy using sheet plastination, frequency of the remaining breast, has been and topographical distribution of performed in selected patients. The tumor foci, which remain in the breast survival rate of BCTh patients is not after BCTh, were evaluated in 131 significantly different when compared patients. to total breast removal, and the local recurrence rate is about 4-8% in five years (Fisher and Wolmark, 1986; MATERIALS AND METHODS Veronesi et al., 1986). In 70-90% of local failures following BCTh, Between 1978 and 1981, modified carcinoma growth was found at the radical mastectomies with full primary tumor site. Four hypotheses axillary dissections were carried out may serve as possible reasons: for invasive carcinomas in 695 patients at the Division of Gynecology (1) Multicentricity is lower than and Obstetrics, University of claimed in the literature. Heidelberg. From this group, 131 (2) Radiotherapy is able to cases were selected which fulfilled sterilize most of the our criteria for breast conserving multicentric tumor foci. therapy. These criteria were as fol1ows:

(3) Multicentric growth occurs intraoperative primarily in the vicinity of - Preoperative and the primary tumor site. tumor size < 3 cm, (4) Excision of the primary tumor - Distance between the tumor and was not performed in sano. areola > 2 cm, 9 Axel Müller

- No preoperative indication for the slices, a connection was multicentric growth, considered to exist. - No known contralateral carcinoma. RESULTS Histological examination, as described by Guhr and co-workers Following simulated quadrant- (1987), was utilized on the formalin- ectomy, carcinomas were found in 42 fixed specimens. Specimens were cut cases (32%), of which 24 (57%) were into 2.5 mm thick slices, stained with invasive carcinomas. The remaining 18 hematoxylin (Well ings and Jensen, cases (43%) were noninvasive. 1973), and completely impregnated with Evaluation of topographical charts a curable clear epoxy and cured (von revealed 15 cases with both residuals Hagens, 1979). By focusing the and multicentric foci. microscope through the full thickness of the slice, microscopic evaluation Multicentric foci, without any through the entire thickness (2.5µ) of connection to the primary tumor, were the slices was possible at magni- found in 24.4% of the cases (32/131). fications up to 100X (Figs, la, 2a). Of these 32 multicentric carcinomas, A three-dimensional picture of 13 (41%) had invasive growth. The relevant alterations was possible by remaining 19 multicentric carcinomas viewing adjacent slices. Suspect (59%) showed noninvasive growth. areas were cut out from the large Residuals of the primary, in the plastinated section and glued on vicinity of the resection line, were wooden blocks; from which 5µ plastic found in 19.1% (25/131) of the cases sections were prepared, restained with and 12 (48%) of these residuals hematoxylin-eosin and examined micro- displayed invasive growth. Thirteen scopically (Figs, lb, 2b). of the 25 residuals (52%) did not show any invasion. Carcinomas found in the specimen were recorded in topographic charts, DISCUSSION thus showing their distribution pattern (Fig. 3). Quadrantectomies Following BCTh, 70-90% of local were simulated within these charts. failures occur in the vicinity of the From these topographic charts, primary tumor (Fisher et al., 1986; "multicentric" tumor foci were those Muller, 1989a; Schnitt et al., 1985). carcinomas which lay outside of the Therefore, the question arises quadrants and had no connection to the "whether the high rate of primary tumor. Carcinomas, which were multicentricity found in the present outside the simulated literature of up to 70% (Gallager, resection area and had a connection to 1969; Morgenstern, 1975) can be the primary tumor, were defined as applied to patients selected for "residuals of the primary tumor". If conservative carcinoma therapy". two invasive tumors were connected by However, since information regarding a noninvasive ductal carcinoma which the size of either the primary tumor was present in all slices and or multicentricity prior to mast- throughout the entire thickness of ectomy is missing in most studies, / Int Soc Plastination, Vol 3, 1989 10 applicability seems unlikely. Rosen in fact, multicentric tumors and co-workers (1975), for example, independent of the primaries. In provided mammographic pictures for practice, through close histological only 50% of their cases. For this examination of resection lines of the present study, only patients suited excised quadrants, BCTh facilitates for BCTh (primary tumor < 3 cm, no both diagnosis of incomplete excision preoperative indication of multi- of the tumor and planning appropriate centricity or bilateral carcinomatous therapy based upon these findings. growth, distance from tumor to areola > 2 cm) were used. Rather than using The necessary differentiation of segmental resection as Muller et al. carcinomas discovered following quad- (1989b), "quadrantectomies" were rantectomy, between "residuals of the simulated in this study. Thus a primary" and actual "independent comparison of rates of carcinomas multicentric foci", is possible only found in remaining breast tissue could through histological examination of be compared with rates found in the the entire breast. literature (usually termed carcinoma foci multicentric, found in quadrants To date, the literature presents not containing the primary tumor). two techniques for the evaluation of the complete breast. Lagios and co- Following quadrantectomy in our workers (1981) and Egan (1982) selected patient group, carcinomas lamellated specimens in 2.5 and 5 mm were observed in 32% of these cases. thick slices, respectively, which were This tumor rate corresponds with then radiographed. The radiographs results of Rosen et al. (1975), Lesser were examined using a magnifier and et al. (1982), and Westman-Naeser et suspect tissue areas were selected for al. (1981) who used chronological further histological evaluation. patient selection and incomplete However, this was time consuming, histological examination (two to three taking one pathologist and two slices from quadrants not containing technicians five years to evaluate 161 the primary tumor). This collection, breasts (Egan, 1982). following chronological hospital admission or surgery dates, includes After staining with hematoxylin, patients who are, however, not suited Wei lings and co-workers (1973, 1975) for BCTh because of tumor diameter, impregnated 2 mm thick tissue slices tumor location, or multicentricity with methyl salicylate. These trans- already diagnosed preoperatively. parent slices were sealed in plastic bags which contained a liquid medium, In order to apply our results to and then evaluated with a magnifier or patients actually having undergone a dissecting microscope at 2-4 X. Any breast conserving therapy, it was not suspect region was excised and only necessary to study a comparable examined histologically following group of patients, but to answer the paraffin impregnation. This pro- question of whether carcinomas cedure is also time consuming, six remaining in the breast following weeks were needed to evaluate one quadrantectomy were simply residuals breast as 300-500 histological slices of incompletely excised primaries, or were prepared. The unpleasant odor of 11 Axel Müller

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<— Legends for color figures: Figure 2a. Photomicrograph of a 2.5 mm thick plastinated breast tissue Figure la. Photomicrograph of a 2.5 slice. The diagnosis is unclear, mm thick plastinated breast tissue proliferative mastopathy with atypical slice with adenosis. 25X. epithelium or noninvasive ductal carcinoma. 25X. Figure lb. Histological section (5Μ) Figure 2b. Histological section (5µ) of the plastinated slice in figure la, from the suspect region in Figure 2a used to confirm diagnosis. used to diagnose ductal carcinoma in Hematoxylin eosin stain. 25X. situ. Hematoxylin eosin stain. 100X.

Figure 3. Topographical chart of a mastectomy specimen. After simulated quadrantectomy, extensions (II) of the primary tumor (I) extend to the resection line, while residuals (III) of the primary tumor extend from the margin of resection and into the remaining breast. A multicentric tumor focus (IV), with partly invasive growth, is observed in the remaining tissue. X = invasive carcinoma, I = noninvasive carcinoma, A and B = resection line of simulated quadrantectomy, C = remaining breast after quadrantectomy, distance between vertical lines = 0.5 cm and between two horizontal lines =1.0 cm. 13 Axel Müller the methyl salicylates necessitates the REFERENCES sealing of tissue slices. With sheet plastination, a breast examination is EGAN RL: Multicentric breast complete within seven days. carcinomas. Clinical-radiographic- pathologic whole organ studies and In our study group, an average of 10-year survival. Cancer 49:1123- 20-25 histological sections 5µ thick 1130, 1982. were prepared per breast. Compared to FISHER B, N Wolmark: Conservative the Well ing's technique, this lower surgery: The American Experience. number of histological slices most Semin Oncol 13:425-433, 1986. likely results from evaluation of the plastinated tissue slices under much FISHER ER, RM Gregorio, C Redmond, F higher magnification (up to 100X). In Vellios, SC Sommers, B Fisher: addition, the solid consistency of the Pathologic findings from the plastinated serial slices allows National Surgical Adjuvant Breast effortless spatial reconstruction of Project (Protocol No. 4). I. any anatomical alteration. Observations concerning the multicentricity of mammary cancer. Sheet plastination allows complete Cancer 35:247-254, 1975. microscopic evaluation of the female FISHER ER, R Sass, B Fisher, R Gre- breast within a short period of time gorio, R Brown, L Wickerham: Path- for even large specimens like: ological findings from the National quadrantectomy or subcutaneous mast- Surgical Adjuvant Breast Project ectomy specimens. Evaluation of our (Protocol 6). II. Relationship of plastinated mastectomy specimens local recurrence to multicentri- revealed residuals of the primary city. Cancer 57:1717-1724, 1986. tumor remaining in 19% of cases evaluated, even with primary tumor GALLAGER HS, JE Martin: Study of size < 3 cm and generous resection mammary carcinoma by mammography through quadrantectomy. This is and whole organ sectioning. Cancer therapeutically relevant, as these 23:855-873, 1969. results suggest the necessity of careful histological examination of GUHR A, A Miiller, HW Anton, G von resection lines of resectates, with Hagens, H Bickley: Complete exam- alteration of therapy according to the ination of specimens using sheet results of this examination. Even plastination with epoxy resin. J then, due to clinically occult Int Soc Plastination 1:23-39, 1987. multicentric tumor foci which may not HOLLAND R, SHJ Veling, M Mravunac, be identifiable even by the best JHCL Hendriks: Histologic multi- histological examinations of the focality of Tis, Tl-2 breast margins of the resectates, irrad- carcinoma. Indication for clinical iation of the entire breast must be trials of breast conserving suggested. surgery. Cancer 56:979-990, 1985. / Int Soc Plastination, Vol 3, 1989 14

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