Benign breast lesions with malignant clinical and mammographic presentations

Benign Breast Lesions with Malignant Clinical and Mammographic Presentations MARC E. KEEN, MD, TARIQ M. MURAD, MD, PHD, MARTIN I. COHEN, MD, AND HAROLD J. MATTHIES, MD Nine cases of benign breast disease in which mammograms had been false-positlve were collected at Northwestern Memorial tIospital. In all but one case the patients had presented initially with questionable masses that required biopsies with requests for frozen section diagnoses. Included in the study were three cases of indurative mastopathy, three cases of fibrocystic disease with sclerosing adenosis, and one case each of sclerosing papillary proliferation, infarcted intraductal papilloma, and fat necrosis with foreign body giant cell reaction. The mammographic and histologic findings for all cases were reviewed. Indurative mastopathy is a poorly known entity with radiologic features highly suggestive of malignancy. As described previously (Cancer 47:561, 1981), the lesion consists of a central nidus of elastosis with irregular projdctions radiating into the adjacent breast tissue. Peripheral areas of the infarcted papilloma and sclerosing papillary proliferation could be confused with infiltrating carcinoma in frozen sections. Familiarity of pathologists with these lesions is essential for avoiding the overdiagnosis of carcinoma. HUM PATIIOL16:1147--1152, 1985. A l t h o u g h t h e d i a g n o s i s o f i n f i l t r a t i n g d u c t a l carcin o m a o f t h e b r e a s t does n o t o f f e r a c h a l l e n g e to m o s t pathologists, b e n i g n lesions t h a t simulate c a r c i n o m a tnay be m o r e p r o b l e m a t i c . S u c h lesions i n c l u d e p a p illary p r o l i f e r a t i o n , 1 m i n i m a l breast c a r c i n o m a , " microglandular adenosis,3, 4 and indurative mastopathy. 5 Diagnostic problems are compounded when these lesions a r e associated with a b n o r m a l m a m m o g r a p h i c a n d clinical p r e s e n t a t i o n s . I n d u r a t i v e mast o p a t h y , as i n d i c a t e d by Rickert et al., 5 c o u l d easily be m i s d i a g n o s e d as c a r c i n o m a . Received from the Departments of Pathology and Radiology, McGaw Medical Center, Northwestern University, Chicago, Illinois. Revision accepted for publication June 3, 1985. Address correspondence and reprint requests to Dr. *lurad: Northwestern Memorial ttospital, Passavant Pavilion, Room 300, 303 East Superior Street, Chicago, IL 60611.

I n tile p r e s e n t s t u d y , tile m a l i g n a n t clincial a n d r a d i o g r a p h i c f e a t u r e s o f b e n i g n hreast lesions w e r e assessed with r e s p e c t to the final diagnoses. I n m o s t cases t h e clinical f e a t u r e s h i g h l y s u g g e s t e d m a l i g n a n c y . F o l l o w - u p m a m m o g r a p h y in all cases indicated that tile lesions w e r e p r o b a b l y o r f r a n k l y m a lignant. Biopsies with f r o z e n section diagnosis were p e r f o r m e d in all cases, a n d tile histologic p a t t e r n s w e r e o f t e n c o n t r o v e r s i a l a n d s u g g e s t i v e o f ntalignancy. W e h a v e a t t e m p t e d to c o r r e l a t e the f e a t u r e s o f false-positive m a m m o g r a n l s with t h e p a t h o l o g i c diagnosis so as to familiarize physicians with these u n usual lesions.

MATERIALS AND METHODS W e r e v i e w e d the h i s t o p a t h o l o g i c f i n d i n g s associated with all false-positive m a m m o g r a m s o b t a i n e d f r o m tile r a d i o l o g i c files at N o r t h w e s t e r n M e m o r i a l H o s p i t a l ( N M H ) , a l a r g e m e t r o p o l i t a n medical c e n t e r with active m a m m o g r a p h y a n d b r e a s t s u r g e r y services. Clinical histories a n d results o f physical e x a m inations were obtained from the patients' charts. F r o z e n sections a n d p a r a f f i n - e m b e d d e d tissue w e r e e x a m i n e d in all cases. A d d i t i o n a l s e c t i o n s w e r e stained with hematoxylin-eosin, Verhoeff-van G i e s o n stain, a n d M a s s o n ' s t r i c h r o m e . O n e lesion, orginally d i a g n o s e d as b e n i g n , was f o u n d to be malign a n t o n r e - e x a m i n a t i o n o f tile material, a n d it was e l i m i n a t e d f r o m the s t u d y .

RESULTS N i n e lesions s i m u l a t i n g c a r c i n o m a w e r e identif i e d in this s t u d y : i n d u r a t i v e m a s t o p a t h y ( t h r e e

TABLE 1. Clinical Features of Patients with False-positive Mammograms

Case

Patient's Age (yr)

1 2 3

62 41 74

4

Presentation

Location of Mass

Size of Mass (cm)

Calcification

Final Diagnosis

+ + +

Indurative mastopathy hlclurative mastopathy Indurative mastopathy

UOQ, right LIQ UIQ

2 x 2 x 1.5 1.5 x 1 x 0.3 1 • 0.8 x 0.3

27

Mass Painfifl mass Mass found at routine mammography Mass

Periareolar, right

1.2 • 1.5 • 0.5

5 6

65 38

Mass Mass

Subareolar, right IQ, right

3 6.5 x 5.5 x 1.5

-

7 8 9

36 41 65

Mass Mass Mass

UQ, left Subareolar, left UQ, left

2 x 2 0.5 3 x 2 x 2.5

+

1147

Sclerosing papillary proliferation Infarcted papilloma Florid sclerosing adenosis Sclerosing adenosis Sclerosing adenosis Fat necrosis, foreign body reaction

HUMAN PATHOLOGY

FIGURE t (top left). Stellate density with tentacles radiating into the surrounding tissue In a pattern similar to that of Infiltrating carcinoma. {Verhoeff-van Gieson stain. Xt0.] FIGURE 2 {top right). Indurative mastopathy with compression and entrapment of ducts showing a pseudolnfiltrative pattern and epitheliosis. [Hematoxylin-eosin stain. X30.] FIGURE 3 {bottom right). Indurative mastopathy with an elastic stain showing dif* fuse positivity with enhanced condensation around ducts. [Verhoeffvan Gieson stain. X30.]

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BENIGN BREASTLESIONS[Keen et al.]

cases); florid sclerosing adenosis (three cases); and sclerosing papillary proliferation, infarcted papilloma, and fat necrosis (one case each). Indurative mastopathy and sclerosing adenosis were the two most common lesions in this study. No specific age distribution was demonstrated, as the youngest patient was 27 and the oldest 74 years of age. Most of the patients had presented with masses that were subsequently evahlated by mammography. In one patient the lesion had been identified by mammography during screening for breast carcinoma. The lesions ranged from 2 to 6 cm in greatest dimension. There was no predilection for any quadrant (table 1). Radiologically, the lesions of indurative mastopathy were characterized by stellate densities with tentacles radiating into the sur~'ounding tissue, similar to those seen in infihrating duct carcinoma. 6 Calcifications observed in two of the three cases were confirmed by histologic examination. Calcification was identified'microscopically in the third case but was not apparent on the n, ammogram. Grossly, the lesions had a gritty texture with a central, slightly depressed center. Microscopically, the lesions consisted of a central focus of connective tissue that radiated into the adjacent breast tissue (fig. 1). At the periphery of the lesions, compression and entrapment of ducts had resulted in a pseudoinfiltrative pattern. These features, in association with adenosis, were consistent characteristics of these lesions and could have led to the mistaken diagnosis of carcinoma, especially on frozen analysis section (fig. 2). All three of these lesions stained intensely with the V e r h o e f f - v a n Gieson elastic stain, both diffilsely throughout the stroma and, in some areas, encircling ducts (fig. 3). The lesion of sclerosing papillary proliferation occurred in the right periareolar area of a 27-yearold patient. T h e mammogram showed a stellate density with infiltrating borders (fig. 4). This lesion had many of the features of indurative mastopathy, but we believe that it can be distinguished from the latter. Grossly, the lesion was a rounded, 1-crn portion of glistening tan-gray tissue. Microscopically, the lesion consisted of a well-defined nodule of disorganized ductal proliferation with a prominent papillary pattern that had been entrapped and disorganized by dense, poorly cellular, fibrous tissue (fig. 5). T h e entrapped ducts showed epitheliosis with benign cytologic features. An elastic stain showed a pattern of periductular positivity as well as focal positivity in the adjacent stroma. The infarcted papilloma showed infiltrating borders on m a m m o g r a p h y and had a positive Le Borgne's sign. 7. At the p e r i p h e r y of the lesion a pseudoinfiltrative pattern mimicked infiltrating car-

FIGURE 4. Mammogram showing a 1-cm Iobufated, Incompletely marginated mass In the lower portion of the right breast, suggestive of malignancy.

cinoma (fig. 6). These lesions were discussed in detail previously, s Mammograms of three lesions of sclerosing adenosis highly suggested malignancy. Grossly, the lesions consisted of irregular masses of finn, slightly fibrotic nodules. Histologic examination revealed dilated ducts, some with epitheliosis and some compressed by a dense stroma, producing a pseudoinfiltrative pattern. The difficulty of diagnosis in such cases is compounded when intraoperative consuhation is requested due to the inferior quality of the slides p r e p a r e d from frozen sections as compared with paraffin-embedded material. The case of fat necrosis with foreign body reaction presented as an upper quadrant mass in a 65year-old patient. T h e mammogram simulated infiltrating carcinoma. T h e gross appearance was that of firm fibroadipose tissue, and histologic examination showed the typical features of fat necrosis, i.e., chronic inflammation and lipid-laden macrophages (fig. 7). DISCUSSION

* A sign of malignancy on x-ray fihn represented by a discrepancy between the palpable breast lesion and the mammographic appearance. The apparent breast lesion is much larger on physical examination than its radiographic inaage.

Indurative mastopathy is a poorly recognized entity that may have clincial and radiologic features highly suggestive of malignancy. The term was first 1149

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Volume 16, No. 11 {November 1985}

FIGURE 5 (left). Sclerosing papillary proliferation entrapped by fibrous tissue. [Hematoxylin-eosin stain. X30.) FIGURE 6 [right]. Infarcted papilloma showing extensive necrosis and pseudoinfiltration. (Verhoeff-van Gieson stain. X50.)

used by Rickert and co-workers5 to describe what they considered a variant of sclerosing papillary proliferation. The most important distinguishing characteristic in their experience was the nature of the duct epithelial proliferation at the periphery of the lesions in the form of adenosis and papillomatosis. They col'rectly i n t e r p r e t e d this lesion as benign and mentioned tile difficuhy of differentiating it from infiltrating carcinoma. A group of similar lesions has been described in the European literature under the name of radial scars.9, to. l,ge confirm the presence of this lesion and consider it a specific entity that may mimic cancer clinically, radiologically, and histopathologically. All reported cases o f indurative mastopathy have come to attention because of their suggestive clinical and radiologic appearance. This lesion should be d i f f e r e n t i a t e d from the rare microglandular adenosis 5,6 and froin tubular carcinoma. The important distinguishing features of tile former include a haphazard proliferation of numerous benign glands

that contain eosinophilic secretory material and are lined by bland cells with vacuolated clear or granular cytoplasm. The stroma is homogeneous and lacks a prominent elastic component. In spite of the prominent elastic component of tubular carcinomas, they can be differentiated from indurative mastopathy on the basis of their malignant histologic features. We have no evidence to support the views of L!nell, et al. 9 and Hamperl, 1~ who consider indurative mastopathy (radial scars) a precursor of tubular carcinoma. The histologic features and the incidence of infarcted papilloma have been described in the literature. 8 The present case was unusual in its frankly malignant clinical and radiologic appearance and positive Le Borgne's sign. Pitfalls in the microscopic diagnosis include an excessive area of necrosis within the center of the lesion and a pseudoinfiltrative pattern along the viable periphery (fig. 6). Identification of the infarcted areal and careful evaluation of the pathologic features at the periphery allow correct di1150

BENIGN BREASTLESIONS(Keen et ol.)

FIGURE 7. Fat necrosis with foreign body reaction, lipid-laden macrophages, and chronic Inflammation. [Hematoxylin-eosin stain.X80.)

agnosis. T h e p e r i p h e r y o f the infarct is characterized "by infiltration a n d maintenance o f d o u b l e layers o f cells, and the cells are cytologically benign. Diagnosis may be d e f e r r e d at the time o f surgical consultation if the possibility o f xnalignancy is entertained. T h e radiographic a p p e a r a n c e o f elastotic breast lesions is not specific, but w h e n the pattern forms a stellate density with finger-like extension into the adj a c e n t tissne, infiltrating carcinoma becomes a significant consideration. Elastosis o f the breast is a usual feature o f breast carcinoma 11 but can also be f o u n d in benign lesions. 12013 Histologically, elastic tissue surr o u n d s ducts and ductules and may be present in both benign and malignant processes. In most breast lesions the elastosis is p r e d o m i n a n t l y p e r i d u c t u l a r and is considered to r e p r e s e n t the condensation o f pre-existing structures by a pathologically d e g e n e r a tive process. This process may have t r a p p e d pre-existing ductules, leading to the pseudoinfiltrative pattern. I n d u r a t i v e m a s t o p a t h y is i m p o r t a n t in that it must be differentiated from carcinoma both radiographically and histologically. Since the radiographic f e a t u r e s a r e n o n s p e c i f i c f o r d i f f e r e n t i a t i o n , this b u r d e n falls to the pathologist, usually at the time o f frozen section analysis. Histologically, care must be exercised not to nfisinterpret the pseudoinfiltrative pattern o f these lesions as the true infiltration o f carcinoma. This can be accomplished by familiarity with the h i s t o p a t h o l o g i c f e a t u r e s o f the lesions, as presented in these cases. Although we agree with Rickert

et al. that indurative mastopathy is a benign lesion, others consider it an incipient tubular carcinoma. 14 F u r t h e r m o r e , in reviewing a large series o f tubular carcinomas, McDivitt et al. 15 did not d e m o n s t r a t e the evolutibn o f tubular carcinoma from indurative mastopathy. 15 Sclerosing papillary proliferation and indurative 9mastopathy share m a n y clinical, radiologic, and histopathologic features. Elastosis was m o r e p r o m i n e n t , however, in indurative nmstopathy and was minimal or absent in o u r case o f sclerosing papillary proliferation. T h e s e two lesions may r e p r e s e n t d i f f e r e n t stages o f the same process. Because the histopathologic f e a t u r e s m a y mimic those o f cancer," the pathologist must have total awareness o f these benign entities to p r e v e n t the overdiagnosis o f cancer.

REFERENCES 1. Fenoglio C, Lattes R: Sclerosing papillary proliferations in the female breast. Cancer 33:691, 1974 2. Gallagher HS, Martin JE: An orientation to the concept of minimal breast carcinoma. Cancer 28:1505, 1971 3. Tavasoli F, Norris It: Microglandular adenosis of the breast: a clinicopathologic stud)' of 11 cases with uhrastructural observations. Am J Surg Pathol 7:731, 1983 4. Rosen P: Microglandular adenosis: benign lesion simulating invasive mammary carcinoma. Am J Surg Pathol 7:137, 1983 5. Rickert R, Kalisher L, Ilutter R: Indurative mastopathy: benign sclerosing lesion of breast with elastosiswhich may simulate carcinoma. Cancer 47:561, 1981 6. Cohen M, Matthies H, Mintzer R, et al: Indurative mastopathy: cause of false positive mammograms. In press, Radiology

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7. LeBorgne R: The Breast in Roentgen Diagnosis. Montevideo, Impresora Uruguaya, 1953 8. Murad T, Contesso G, Mouriesse ti: Papillary tumors of large lactiferous ducts. Cancer 48:122, 1981 9. Linell F, Ljungberg O, Anderson I: Breast carcinoma: aspects of early stages, progression and related problems. Acta Pathol Microbiol Scand [A] (suppl):272, 1980 10. tlamperl H: Strahlige Narben und oblitierende Mastopathie. Virchows Arch [A] 369:55, 1975 11. Azzopardi J, Lanrini R: Elastosis in breast cancer. Cancer 33:174, 1974

12. Azzopardi JG: Problems in Breast Pathology. London, WB Saunders Co, 1977, pp. 379-394 13. "Fremblay G, Buell R, Seemayer T: Elastosis in benign sclerosing ductal proliferation of tile female breast. Am J Surg Pathol 2:155, 1977 14. Fisher ER, Palekar AS, Kotwal N, et al: A nonencapsulated sclerosing lesion of the breast. Am J Clin Pathol 71:240, 1979 15. McDivitt R, Bo)'ce W, Gersell D: Tubular carcinoma of the breast: clinical and pathologic observation concerning 135 cases. Am J Surg Pathol 6:401, 1982

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