Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

1. E. How will you approach the 55-year old menopausal patient with a 2-cm diameter, mobile, firm, non-tender mass on her R breast?

2. Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

3. 1. Role of imaging modality • Breast imaging techniques are used to detect small, nonpalpable breast abnormalities, evaluate clinical findings, and guide diagnostic procedures. • Mammography • The primary imaging modality for screening asymptomatic women • Ideal and indispensable for women older than 40 years, for whom the risk of breast cancer is increased. • Ultrasonography • Useful in determining whether a lesion detected by other modalities is solid or cystic and in determining contour and internal properties of a lesion • Not a useful screening modality http://www.emedicinehealth.com/mammogram/article_em.htm#Mammogram Introduction

4. 2. Diagnosis • Ultrasonography is used to distinguish solid from cystic structures. • Simple cysts are seen on sonograms as round or oval with sharply defined margins and posterior acoustic enhancement.  • Complex cysts are characterized by a significant solid component, septations, lobulations, varied wall thickness, and the presence of internal debris.  • Abscesses usually appear as ill-defined masses and have central hypoechoic areas with either septations or low-level internal echoes, and posterior enhancement. • Townsend: Sabiston Textbook of Surgery, 18th ed

5. 2. Diagnosis • Fine-needle aspiration (FNA) has become a routine part of the physical diagnosis of breast masses. • Differentiates solid from cystic masses, but it may be done whenever a new dominant, unexplained mass is found in the breast. • Postponed only if mammography is necessary and might confuse the radiographic evaluation. • Cyst fluid is usually turbid and dark green or amber and can be discarded if the mass totally disappears and the fluid is not bloody. • By using FNA in routine examination of the breast, unnecessary open biopsy of cystic change is avoided. • Townsend: Sabiston Textbook of Surgery, 18th ed

6. 2. Diagnosis • FNAC • If the mass is solid and the clinical situation is consistent with carcinoma, cytologic examination of the aspirated material is performed. • The presence of carcinoma cells on FNA does not differentiate between in situ and invasive breast cancer. • A positive result allows informed discussions with the patient, definite plans for treatment, and appropriate consultations or second opinions. • Townsend: Sabiston Textbook of Surgery, 18th ed

7. 2. Diagnosis • Open biopsy. Carcinoma will not be missed if a surgical biopsy is done when: • (1) needle aspiration produces no cyst fluid and a solid mass is diagnosed • (2) the cyst fluid produced is thick and blood tinged • (3) fluid is produced but the mass fails to resolve completely • Other surgeons have added frequent reappearance of the cyst in the same location and rapid reaccumulation of fluid after initial aspiration (within a few days). • Townsend: Sabiston Textbook of Surgery, 18th ed

8. 3. FNAC reveals NEGATIVE FOR MALIGNANT CELLS. How would you now manage the patient?

9. Radial scars are benign pseudoinfiltrative lesions of uncertain significance. They are characterized by a fibroelastotic core with entrapped ducts, surrounded by radiating ducts and lobules displaying variable epithelial hyperplasia, adenosis, duct ectasia, and papillomatosis. Dx: Mammography Tx: excision • When the stroma involutes too quickly, alveoli remain and form microcysts, which are precursors of macrocysts. Macrocysts are common, are often subclinical in nature, and do not require specific treatment. http://www.health.am/cr/more/benign-breast-diseases-classification-diagnosis/P2/

10. 3. FNAC reveals NEGATIVE FOR MALIGNANT CELLS. How would you now manage the patient?

11. Case 3: A 55-year old female consults because of bloody nipple discharge.

12. Differentiate a physiologic from pathologic nipple discharge. • The first step in the evaluation of a nipple discharge • Physiologic Discharge: • Characterized by discharge only with compression and by multiple duct involvement • Frequently bilateral • Can be identified with careful history • Work-up: Complete breast examination, with mammography in women more than 35 years old • Negative work-up: reassurance is the only therapy that is needed. Because stimulation of the nipple (i.e., squeezing to check for discharge) actually promotes discharge, patients with a physiologic discharge should be advised to avoid checking for discharge. • Often resolves when the nipple is left alone. • Pathologic Discharge Morrow, Monica. 2000. The evaluation of common breast problems. <http://www.aafp.org/afp/20000415/2371.html>

13. Differentiate a physiologic from pathologic nipple discharge. • The first step in the evaluation of a nipple discharge • Physiologic Discharge • Pathologic Discharge: • If they are spontaneous, bloody or associated with a mass • Usually unilateral and confined to one duct • Most common cause: intraductalpapilloma, followed by duct ectasia • If a palpable mass is present, the likelihood of cancer is greatly increased. Morrow, Monica. 2000. The evaluation of common breast problems. <http://www.aafp.org/afp/20000415/2371.html>

14. http://www.merck.com/mmpe/sec18/ch253/ch253c.html

15. Nipple discharges • Milky • Bloody or serous Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

16. Nipple discharges • Milky • Associated with increased production of prolactin (e.g., by a pituitary adenoma), hypothyroidism, or endocrine anovulatory syndromes. • Can also occur in patients taking oral contraceptives, tricyclic antidepressants, methyldopa, or phenothiazines. • Repeated nipple stimulation can also induce lactation • Has not been associated with malignancy • Bloody or serous Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

17. Nipple discharges • Milky • Bloody or serous • Most commonly associated with benign lesions but, rarely, can be due to a malignancy • A normal bloody discharge can also occur during pregnancy, possibly due to the rapid formation of new lobules Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

18. Bilateral Nipple Discharge • Suggestive of a benign condition if: • Bilateral and multiductal in origin • Occurs in women age 39 years or less • Milky or blue green in color. • Prolactin-secreting pituitary adenomas are responsible for bilateral nipple discharge in less than 2% of cases. Unilateral Nipple Discharge • Suggestive of cancer if: • Spontaneous, unilateral, localized to a single duct • Occurs in women age 40 years or more • Bloody, or associated with a mass Schwartz’s Principles of Surgery, 8th ed.

19. Discharge in Association with Malignancy • The risk of malignancy with discharge increases with age. • Discharge is associated with carcinoma in 7% of women younger than 60 years and in 30% of women older than 60 years. • The most common etiologies for discharge are a solitary large duct papilloma, cysts, or carcinoma. • Carcinomas presenting as nipple discharge not associated with a palpable mass are equally divided between invasive and in situ carcinomas • There is considerable interest in developing the cytologic examination of induced nipple discharge into a screening test for breast cancer. Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

20. Kumar et al: Robbins & Cotran Pathologic Basis of Disease 7E

21. Benign Causes of Bloody Discharge Papillomas • Solitary intraductalpapillomas are true polyps of epithelium-lined breast ducts. • Solitary papillomas are most often located close to the areola but may be present in peripheral locations. • Most are less than 1 cm but can grow to as large as 4 or 5 cm. Larger papillomas may appear to arise within a cystic structure, probably representing a greatly expanded duct. • Not associated with an increased risk for breast cancer. • Often accompanied by bloody nipple discharge. Less frequently, they are discovered as a palpable mass under the areola or as a density lesion on a mammogram. • For peripheral papillomas, the differential diagnosis is between papilloma and invasive papillary carcinoma. Papillomatosis • Refers to epithelial hyperplasia, which commonly occurs in younger women or is associated with fibrocystic change. This lesion is not composed of true papillomas. • The hyperplastic epithelium in papillomatosis may fill individual ducts like a true polyp but has no stalk of fibrovascular tissue. Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

22. Benign Causes of Bloody Discharge Mycotic Infections • Rare • Usually involve blastomycosis or sporotrichosis. • Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infections, which present as mammary abscesses in close proximity to the nipple–areola complex. • Pus mixed with blood may be expressed from sinus tracts. Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

23. Benign Causes of Bloody Discharge Mammary duct ectasia • Occurs most often in women in their 40s and 50s and affects as many as one in four women during or after menopause. • A subareolarperiductal chronic inflammatory process that in early stages is characterized by dilated ducts but eventually produces ductal obliteration

24. Describe how you would localize the involved duct. Ductography • Primary indication: nipple discharge, particularly when the fluid contains blood. • Procedure: • Radiopaque contrast media is injected into one or more of the major ducts and mammography is performed. A duct is gently enlarged with a dilator and then a small, blunt cannula is inserted under sterile conditions into the nipple ampulla. With the patient in a supine position, 0.1 to 0.2 mL of dilute contrast media is injected and CC and MLO mammography views are obtained without compression. • Intraductalpapillomas are seen as small filling defects surrounded by contrast media • Cancers may appear as irregular masses or as multiple intraluminal filling defects Schwartz’s Principles of Surgery, 8th ed.

25. Ductogram. A. Craniocaudal and (B) mediolateral oblique mammography views demonstrate a mass (arrows) posterior to the nipple and outlined by contrast, which also fills the proximal ductal structures. (Courtesy of Dr. B. Steinbach.) Schwartz’s Principles of Surgery, 8th ed.

26. Patient’s Ductogram

27. Diagnosis • Hemoccult tests • Cytologictests of the fluid • Sonography • Magnetic resonance imaging • Fiber-ductoscopy • Excisional biopsy Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

28. Diagnosis • Hemoccult tests can be used to assess the nipple discharge fluid in order to confirm or exclude the presence of occult blood. • Cytologictests of the fluid can be performed; the sensitivity of fluid cytology is low (<15%), but the specificity has been 100% when malignant cells were confirmed on fluid cytology. • Sonographyis not typically used unless the nipple discharge is accompanied by a palpable mass or a positive mammographic finding. Sonography may be useful in presurgical localization if galactography reveals a dilated duct larger than a few millimeters in width. Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

29. Diagnosis • Magnetic resonance imaging may play an adjunctive role, aiding in the differentiation of benign ductal abnormalities from malignant ones. • Fiber-ductoscopyis an experimental technique that may eventually play a role in the evaluation of nipple discharge. • Procedure: At this endoscopic examination, a thin, flexible, silica fiber-ductoscope is inserted into the duct through the secreting duct orifice at the surface of the nipple; the intraluminal findings are viewed on a television monitor. • Makes it possible to have not only cytology specimens but also tissue samples for histologic assessment of intraductal lesions visualized through ductoscopy Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

30. Diagnosis • Excisionalbiopsy of the offending duct and any mass lesionis the definitive diagnosis. A 3.0 lacrimal duct probe is used to identify the duct that requires excision. Schwartz’s Principles of Surgery, 8th ed.

31. Limitations of Techniques • Galactographyis not indicated unless the nipple discharge is spontaneous, unilateral, and expressed from a single pore. • MRI and fiber-ductoscopy remain experimental techniques in the evaluation of nipple discharge. Further studies are required before their roles are determined. Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>

32. Treatment • All patients with spontaneous or unilateral nipple discharge should be referred for surgical evaluation. This is true for patients with bloody discharges and for those with clear or serous discharges. • A terminal duct excision is both diagnostic and, for discharges that turn out to have a benign cause, therapeutic. Schwartz’s Principles of Surgery, 8th ed.

33. Papillomas: Treatment is excision through a circumareolar incision. • Mycotic infection: Amphotericin B (systemic) eliminates the necessity of surgical intervention, but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. For Candida infections, therapy involves the removal of predisposing factors such as maceration and the topical application of nystatin. Azavedo. 2009. Breast, Nipple Discharge Evaluation. <http://emedicine.medscape.com/article/347305-overview>