Fibrocystic Change and Duct Ectasia
Fibrocystic Change and Duct Ectasia
Contents
3.1 Fibrocystic Change . . . 16
3.1.1 Definition . . . 16
3.1.2 Synonyms . . . 16
3.1.3 Etiology . . . 16
3.1.4 Macroscopy . . . 16
3.1.5 Microscopic Features . . . 16
3.1.6 Additional Comments . . . 16
3.1.7 Further Reading . . . 17
3.2 Duct Ectasia (Periductal Mastitis) . . . 17
3.2.1 Definition . . . 17
3.2.2 Synonyms . . . 17
3.2.3 Etiology and Pathogenesis . . . 17
3.2.4 Macroscopy . . . 17
3.2.5 Microscopic Features . . . 17
3.2.6 Further Reading . . . 18
Caution
● Fibrocystic change (FCC) without hyperplasia is not associat- ed with an increased cancer risk. The designation of FCC should be restricted to lesions not associated with moderate to severe epithelial hyperplasia [11, 12].
● FCC represents an alteration of terminal duct-lobular units or intralobular glands. This condition should be clearly distin- guished from duct ectasia, which is a disease of larger (ex- tralobular) ducts (see section on duct ectasia) [2].
● Migrations of foam cells into the epithelial cell layers of cysts may mimic a pagetoid appearance of lobular intraepithelial neoplasia (pseudopagetoid appearance).
● Cysts that contain cell debris with fragmented, inhomoge- neous secretory material should be examined at higher mag- nifications to exclude the possibility of intraepithelial neo- plasia of flat type (see section on DIN flat type) [2].
● Apocrine metaplasia can be associated with significant cyto- logic atypia. To qualify as atypical apocrine metaplasia, the nuclei should at least reveal a threefold variation in size often with irregular chromatin distribution. The presence of promi- nent nucleoli is a common finding in ordinary apocrine meta- plasia and, therefore, should not be used as an indication of atypicality.
3.1.6 Additional Comments
About one-third of women between 20 and 45 years of age show some clinical evidence of FCC. Histologically, FCC can be identi- fied in about 55% of autopsies of women with clinically normal breasts [3, 6, 7, 11, 12].
FCC is frequently a multifocal, bilateral mammary alteration.
It can cause premenstrual breast swelling or tenderness of 1 week’s duration or can be associated with multiple hard, tender nodules. Permanent breast pain and tenderness can be the prominent clinical features of FCC in women 40–50 years of age [7, 10, 16].
FCC with atypical apocrine metaplasia seems to be associated with significant increased risk for breast cancer in women older than 60 years (elevated relative risk of 5.5 within 5.6 years of follow-up) [14].
Apocrine metaplastic cells are characteristically negative for ER and PR. They, however, are typically immunopositive for androgen receptors [15].
3.1 Fibrocystic Change
3.1.1 Definition
A benign alteration of the breast consisting of cystic dilatation of intralobular glands (terminal duct-lobular unit) with or without stromal fibrosis. Fibrocystic changes include apocrine metapla- sia, mild epithelial hyperplasia, and mild degrees of adenosis.
3.1.2 Synonyms
There are several designations for fibrocystic change (FCC), such as fibrocystic disease, fibrous (fibrocystic) mastopathy, mamma- ry dysplasia, and fibroadenosis cystica. The term “fibrocystic change” is the most appropriate one because it underlines an ex- aggerated physiologic phenomenon rather than a disease [3, 6, 7, 11, 12].
3.1.3 Etiology
Hormonal imbalances with a predominance or relative excess of estrogens [8, 16].
3.1.4 Macroscopy
Several clear or blue-domed cysts with a diameter of 1–2 mm (microcysts). Occasionally, larger cysts of 1–2 cm in diameter (macrocysts). Greyish-white cut surface with firm consistency.
3.1.5 Microscopic Features
(Fig. 2)● Round to ovoid cystically dilated spaces lined by one or two cell layer(s) of epithelial cells and attenuated myoepithelial cells.
● Apocrine metaplasia is a common finding. The apocrine metaplastic cells show abundant eosinophilic granular cyto- plasm and round nuclei with prominent nucleoli. The cells often show a columnar configuration and display luminal cytoplasmic projections or “apical snouts.”
● Sclerotic changes of the intralobular stroma may be promi- nent. In contrast to duct ectasia, the cysts and sclerotic areas do not contain elastic tissue.
● Rupture of the cysts with inflammatory reaction may be pres- ent.
● Microcalcifications are present in the lumens of cysts or with- in the connective tissues.
● A mild degree of adenosis or microscopic expansion of the lobules by an increase in the number of acinar structures per lobule can be present [1, 2, 3, 16].
Chapter 3 17
Fibrocystic Change and Duct Ectasia
3.1.7 Further Reading
1. Anastassiades OTH, Tsakraklides E, Gogas J. The histology of fibro- cystic disease of the female breast. Pathol Res Prac 1981;172:109–
129.
2. Azzopardi JG. Problems in breast pathology. WB Saunders, Philadel- phia, 1979, pp. 57–72.
3. Bartow SA, Black WC, Waeckerlin RW, et al. Fibrocystic disease: a continuing enigma. Pathol Annu 1982;17:93–111.
4. Ciatto S, Biggeri A, Rosselli Del Turco M, et al. Risk of breast cancer subsequent to proven gross cystic disease. Eur J Cancer 1990;26:
555–557.
5. Davis HH, Simons M, Davis JB. Cystic disease of the breast: relation- ship to carcinoma. Cancer 1964;17:957–978.
6. Drukker BH, deMendonca WC. Fibrocystic change and fibrocystic disease of the breast. Obstet Gynecol Clin North Am 1987;14:
685–702.
7. Fiorica JV. Fibrocystic changes. Obstet Gynecol Clin North Am 1994;21:445–452.
8. Golinger RC. Hormones and the pathophysiology of fibrocystic mastopathy. Surg Gynecol Obstet 1978;146:273–281.
9. Haagensen DE Jr. Is cystic disease related to cancer? Am J Surg Pathol 1991;15:687-694.
10. Hockenberger SJ. Fibrocystic breast disease: every woman is at risk.
Plast Surg Nurs 1993;13:37–40.
11. Hutter RVP. Consensus Meeting: Cancer Committee of the College of American Pathologists: is “fibrocystic disease” of the breast pre- cancerous? Arch Pathol Lab Med 1986;110:171–173.
12. Love SM, Gelman RS, Silen W. Fibrocystic “disease” of the breast – a non-disease. N Engl J Med 1982;307:1010–1014.
13. Page DL, Vander Zwag R, Rogers LW, et al. Relation between compo- nent parts of fibrocystic disease complex and breast cancer. J Natl Cancer Inst 1978;61:1055-1063.
14. Seidman JD, Ashton M, Lefkowitz M. Atypical apocrine adenosis of the breast: a clinicopathologic study. Cancer 1996;77:2529–2537.
15. Tavassoli FA, Purcell CA, Bratthauer GL, et al. Androgen receptor ex- pression along with loss of bcl-2, ER, and PR expression in benign and malignant apocrine lesions of the breast: implications for ther- apy. Breast J 1996;4:261–269.
16. Vorherr H. Fibrocystic breast disease: pathomorphology, clinical picture, and management. Am J Obstet Gynecol 1986;154:161–179.
17. Wu C, Ray RM, Lin MG, et al. A case-control study of risk factors for fibrocystic breast conditions: Shanghai Nutrition and Breast Dis- ease Study, China, 1995–2000. Am J Epidemiol 2004;15:945–960.
3.2 Duct Ectasia (Periductal Mastitis)
3.2.1 Definition
A relatively common disease of extralobular ducts with irregular dilatation, periductal fibrosis, and/or inflammation.
3.2.2 Synonyms
Periductal mastitis, plasma cell mastitis, comedo mastitis, masti- tis obliterans.
3.2.3 Etiology and Pathogenesis
Three possibilities exist [1, 5, 6, 14]:1. Ductal dilatation as the initial phase of the disease due to endocrine abnormalities (hyperprolactinemia?)
2. Periductal inflammation, not ductal dilatation, as the initial and essential pathological manifestation of the disorder 3. Secondary duct ectasia proximal to intraductal proliferations
such as central papilloma
3.2.4 Macroscopy
A single cystic space or multiple dilated structures containing thick or creamy yellow to white material sometimes closely re- sembling “comedo” necrosis [19]. Thickening and irregularity of the skin and nipple inversion are not infrequent [12, 20, 21].
3.2.5 Microscopic Features
(Fig. 3)● Periductal (large duct) lymphoplasmacytic infiltration
● Periductal fibrosis
● Irregular dilatation and obliteration of ducts
● Lipid-filled foam cells (macrophages) in the ductal lumina;
eosinophilic inspissated luminal contents
● Intense neutrophilic granulocyte infiltration by acute phase of duct ectasia
● Total obliteration of the ductal lumen by fibrous tissue, with complete disappearance of the epithelial lining (mastitis oblit- erans) at the end stage
● “Recanalization” of obliterative duct ectasia: epithelial regen- eration of the occluded duct, forming a single channel or grouped channels with penetration longitudinally into the fibrous plug
● Cystic disease and duct ectasia in combination; in practice, cystic disease and duct ectasia are not infrequently seen together in the same breast [1, 6, 19]
Caution
●Duct ectasia (periductal mastitis) differs from (fibro)cystic change clinically, histopathologically, pathogenetically, and probably also etiologically. Duct ectasia can be associated with nipple abnormalities and may clinically simulate carcino- ma. Pathologists should not misinterpret duct ectasia as FCC [1, 7, 9, 10, 12, 16, 20] (see Table 3.1).
3.2.6 Further Reading
1. Azzopardi JG. Problems in breast pathology. WB Saunders, Philadel- phia, 1979, pp. 57–87.
2. Browning J, Bigrigg A, Taylor I. Symptomatic and incidental mam- mary duct ectasia. J R Soc Med 1986;79:715–716.
3. Chinoy R, Talvalkar GV. Mammary duct ectasia. Indian J Cancer 1981;18:128–133.
4. Dixon JM. Periductal mastitis/duct ectasia. World J Surg 1989;13:
715–720.
5. Dixon JM, Anderson TJ, Lumsden AB, et al. Mammary duct ectasia.
Br J Surg 1983;70:601–603.
6. Haagensen CD. Diseases of the breast, 3rd edn. WB Saunders, Philadelphia, 1986, pp. 357–368.
7. Haagensen CD. Mammary duct ectasia – a disease that may simulate carcinoma. Cancer 1951;4:749–761.
8. Huynh PT, Parellada JA, de Paredes ES, et al. Dilated duct pattern at mammography. Radiology 1997;204:137–141.
9. Leung AK, Kao CP. Mammary duct ectasia: a cause of bloody nipple discharge. J Natl Med Assoc 2004;96:543–-545.
10. Miller SD, McCollough ML, DeNapoli T. Periductal mastitis mas- querading as carcinoma. Dermatol Surg 1998;24:383–385.
11. Rahal RM, de Freitas-Junior R, Paulinelli RR. Risk factors for duct ectasia. Breast J 2005;11:262–265.
12. Rees BI, Gravelle H, Hughes LE. Nipple retraction in duct ectasia. Br J Surg 1977;64:577–580.
13. Sandison AT, Walker JC. Inflammatory mastitis, mammary duct ectasia, and mammary fistula. Br J Surg 1962;50:57–64.
14. Shousha S, Backhouse CM, Dawson PM, et al. Mammary duct ecta- sia and pituitary adenomas. Am J Surg Pathol 1988;12:130–133.
15. Stringel G, Perelman A, Jimenez C. Infantile mammary duct ectasia:
a cause of bloody nipple discharge. J Pediatr Surg 1986;21:671–674.
16. Sweeney DJ, Wylie EJ. Mammographic appearances of mammary duct ectasia that mimic carcinoma in a screening programme. Aus- tralas Radiol 1995;39:18–23.
17. Tedeschi LG, McCarthy PE. Involutional mammary duct ectasia and periductal mastitis in a male. Hum Pathol 1974;5:232–236.
18. Thomas WG, Williams RCN, Davies JD, et al. The clinical syndrome of mammary duct ectasia. Br J Surg 1982;69:423–425.
19. Tice GE, Dockerty MB, Harrington WS. Comedomastitis. A clinical and pathologic study of data in 172 cases. Surg Gynecol Obstet 1948;51:350–355.
20. Walker JC, Sandison AT. Mammary-duct ectasia. A clinical study. Br J Surg 1964;51:350–355.
21. Webb AJ. Mammary duct ectasia-periductal mastitis complex. Br J Surg 1995;82:1300–1302.
3
Table 3.1. Major differences between (fibro)cystic change and duct ectasia, modified from Azzopardi [1] (TDLU terminal duct-lobular unit)
Cystic change Duct ectasia
Mainly lobular (TDLU) alteration Ductal disease
Affects any part of breast Mainly affects major ducts and subareolar ducts
No nipple discharge Nipple discharge in about 20% of those with clinical disease
No nipple retraction Nipple retraction common due to periductal fibrosis
No inflammatory disease except ruptured cysts Usually periductal chronic inflammation Can be associated with epithelial hyperplasia Usually no epithelial hyperplasia
Cysts rounded or ovoid with thin yellow to brown contents Irregularly dilated ducts with thin contents initially, followed by creamy (“comedo” type) contents; other ducts obliterated partially or completely by fibrous plug
No elastic layers in cyst walls (TDLU) Usually elastica in ductal wall (elastic tissue stains)
Epithelial lining usually apocrine Apocrine metaplasia very rare
Mammographic calcification more amorphous, Calcification common in periductal fibrosis, producing tubular, scattered and not in line of ducts annular, and linear shadows on mammogram
Chapter 3
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20 Fibrocystic Change and Duct Ectasia
Fig. 2: Apocrine metaplasia.
Fig. 2.1: A cyst lined by one layer of cells showing deeply eosinophilic cytoplasm and round nuclei.
Fig. 2.2: Immunohistochemically, apocrine meta- plastic cells are characteristically positive for andro- gen receptors. They are, however, almost always negative for estrogen receptors and progesterone receptors (not shown).
Fig. 2.3 and 2.4: Imprint cytology showing clusters of apocrine metaplastic cells with abundant cyto- plasm, round nuclei, and prominent nucleoli. Note the presence of numerous cytoplasmic granules (Diff-Quik stain).
Fig. 2.5 and 2.6: Imprint cytology of a cyst shows cohesive clusters of apocrine metaplastic cells with eosinophilic or amphophilic cytoplasm and round, uniform nuclei (Papanicolaou stain).
Fig. 2.7: A cystically dilated duct lined by multiple layers of apocrine metaplastic cells. This is an exam- ple of intraductal apocrine hyperplasia.
Fig. 2.8: Higher magnification of apocrine meta-
plastic cells displays eosinophilic, granular cyto-
plasm.
Chapter 3
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22 Fibrocystic Change and Duct Ectasia
Fig. 3: Duct ectasia.
Case history: A 50-year-old woman presented with a hard and irregular mass in her left breast. She had a bloody nipple discharge and inflammatory skin changes. The clinical and mammographic findings were highly suspicious for malignancy (inflamma- tory breast carcinoma?). Excisional biopsy of the lesion was performed.
Fig. 3.1: Dilated ducts containing eosinophilic secretory material.
Fig. 3.2: While some ducts are irregularly dilated, others show marked periductal fibrosis and luminal obstruction.
Figs. 3.3 and 3.4: Duct ectasia with marked
periductal lymphoplasmacytic infiltration (chronic
periductal mastitis).
Chapter 3
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24 Fibrocystic Change and Duct Ectasia
Figs. 3.5 and 3.6: Periductal histiocytic infiltration with numerous fibroblasts in duct ectasia causing obliteration of the involved ducts (obliterative phase of duct ectasia).
Fig. 3.7: An ectatic duct containing cellular debris combined with secretory material.
Fig. 3.8: Some of the involved ducts show reactive epithelial cell alterations characterized by enlarge- ment of the nuclei, higher nuclear-cytoplasmic (N/C) ratio, and prominent nucleoli.
Figs. 3.9 and 3.10: Van Gieson elastica stain in duct ectasia revealing either continuous or discontinu- ous elastic tissue in large (extralobular) ducts.
Fig. 3: Final remarks
●
This case demonstrates that duct ectasia may appear clinically and mammographically as a tumor. Duct ectasia with inflammatory skin changes, nipple discharge, and nipple inver- sion can easily be mistaken for cancer, particu- larly inflammatory breast carcinoma.
●
The involved ducts in duct ectasia may show epithelial cell alterations with significant reac- tive changes such as nuclear enlargement, higher N/C ratio, and prominent nucleoli.
These alterations should not lead to misinter- pretation as atypical ductal hyperplasia or ductal carcinoma in situ.
●
