Histopathological Evaluation of Patients With Fibrocystic Breast Disease in Fetha

Histopathological Evaluation of Patients With Fibrocystic Breast Disease in Fetha

Fibrocystic breast disease also called fibrocystic breasts or fibrocystic change is a benign (non-cancerous) condition in which a woman has painful lumps in one or both breasts due to palpable small breast masses or breast cysts. Fibrocystic breast disease is a condition of breast tissue affecting an estimated 30-60% of women and at least 50% of women of child bearing age (Susan, 1990).

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It is characterized by non-cancerous breast lumps which can sometimes cause discomfort, often periodically related to hormonal influences from the menstrual cycle (University of Maryland Medical Center (Overview, 2012). In ICD-10 (international statistical classification of disease and related health problem), the condition is called diffuse cystic mastopathy or if there is epithelial proliferation, fibrosclerosis of breast. Other names for this condition include chronic cystic mastitis, fibrocystic mastopathy and mammary dysplasia (Atlantic women specialist, 2012). The condition has also been named after several people since it is a very common disorder, some authors have argued that it should not be termed a disease (Santen et al., 2005) whereas others fee, that it meets the criteria for a disease, it is not a classic form of mastitis (breast inflammation), (ultrasound characteristic of breast masses, 2009).
The changes in fibrocystic breast disease are characterized by the appearance of fibrous tissue and a lumpy, cobblestone textures in the breasts. These lumps are smooth with defined edges and are usually free moving in regard to adjacent structures. The lumps are most often found in the upper outer sections of the breast (nearest to the armpit). Women with fibrocystic changes may experience a persistent or intermittent breast aching or breast tenderness related to periodic swelling. Breast and nipples may be tender or itchy (Sakorafas, 2001).

A fibrocystic breast change is a cumulative process caused partly by the normal hormonal variation during a woman’s monthly cycle. The most important of these hormones are estrogen, progesterone and prolactin. These hormones directly affect the breast tissue by causing cells to grow and multiply (fibrocystic breast condition, 2010). Many other hormones such as thyroid stimulating hormone (TSH), insulin, growth hormone and growth factors such as TGF-beta exert direct and indirect effects amplifying or regulating cell growth(Rosen,2001). Years of such fluctuations eventually produce small cyst and or areas of dense or fibrotic tissue. Multiple small cysts and an increasing level of breast pain commonly develop when a woman hits her 30’s. Larger cysts usually do not occur until after the age of 35 (fibrocystic breast condition, 2010).
Several variants of fibrocystic breast changes may be distinguished and these may have different causes and genetic predispositions. Adenosis involves abnormal count and density of lobular units, while other lesions appear to stern mainly from ductal epithelial origins (Cann et al., 2000). There is preliminary evidence that iodine deficiency contributes to fibrocystic breast changes by enlarging the sensitivity of breast tissue to estrogen (Joseph et al, 2012). Diagnosis of fibrocystic breast disease is mostly done based on symptoms after exclusion of breast cancer. Nipple fluid aspiration can be used to classify cyst type (and to some extent improve breast cancer risk prediction) but it is rarely used in practice. Biopsy or fine needle aspirations are rarely warranted (Benign breast cancer, 2002). Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast examination and on a physical examination. During this examination, the doctor checks for unusual areas in the breasts, both visually and manually. Also the lymph nodes in the axilla areas and lower neck are examined. In order to establish whether the lump is a cyst or not, several imaging tests may be performed.

The breast biopsy is usually the test used to confirm the suspected diagnoses. There are different types of breast biopsies that may be performed viz: A fine needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst (diagnosing fibrocystic breast, 2010). This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into the hard tissue to find lump. The core-needle biopsy is normally performed under local anesthesis and in physician’s office. The needle used in this procedure is slightly larger than the one used for a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination. A newer type of breast biopsy is the stereotactic biopsy that relies on a three dimensional x-ray to guide the needle biopsy of non-palpable mass.

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AIM
The aim of this study is to evaluate the prevalence rate of fibrocystic breast disease (FBD), in the Federal Teaching Hospital Abakaliki (FETHA-2) and to characterize the type that can progress to cancer.

OBJECTIVES
To characterize the type of FBD that could lead to lead to cancer.
To determine the age-group where breast fibrosis occurs most.
To determine if breast fibrosis is influenced by number of birth(parity)

CHAPTER TWO
LITERATURE REVIEW
The presence of a lump in the breast is a great cause of anxiety, apprehension, and uncertainty to most patients. This may be accrued to the increasing public awareness of breast cancer which is presently the most common female malignancy worldwide (Parkin et al., 2002). Nevertheless the vast majority of breast lesions are benign, (Yusufu et al., 2003). Fibrocystic breast disease or benign breast diseases (BBD), however, constitute a heterogeneous group of disorders including developmental abnormalities, epithelial and stromal proliferations, inflammatory lesions, and neoplasms (Tavassoli and Devilee, 2003).
While most reports indicate that breast lumps are predominantly benign and mostly nonproliferative epithelial lesions, there has, however, been increasing recognition of the risk implications of the various forms of premalignant lesions (Jensen et al, 1989). Researchers widely believe that cancer risk is increased in patients with atypical ductal and atypical lobular hyperplasia (Dupont et al., 2006) reported a relative risk of 3.1 for subsequent breast cancer in women with atypical lobular hyperplasia. A four- to fivefold increased risk for breast cancer has been associated with atypical ductal hyperplasia mostly in the ipsilateral breast within 10-15 years of diagnosis (Hartmann et al, 2005). It is therefore pertinent for pathologists, oncologists, and radiologists not only to recognize and distinguish FBD (Fibrocystic breast disease) from breast cancer but also to have in depth knowledge of the pattern of occurrence of these disorders in their geographical locale.
Fibrocystic changes is a common type of benign condition accounted for about 23.8% of cases (Anyikam et al., 2008), a figure consistent with the 22.9 and 27.7% documented in Enugu and Port Harcourt respectively (Adeniji et al., 1997). A much higher figure of 42.2% was however reported in Ilesha and of note (Ochicha et al., 2002), fibrocystic change was reported as the commonest BBD in Kano comprising 34.3% of cases (Adesunkanmi and Agbakwuru, 2001). In Italy and in another study in the USA (Ciatto et al., 1999), fibrocystic change was also the commonest BBD accounting for 43.2 and 47% of cases respectively (Donegan and Spratt, 1995).
Fibrocystic change seems relatively more common in Pakistanis as (Memmon et al., 2007) reported a high frequency of 66.3% and observed a changing trend of benign tumors from fibroadenoma to fibrocystic change.

Fibrocystic change consists of a spectrum of morphological changes comprising cysts, adenosis epithelial hyperplasia, and fibrosis (Ciatto et al., 1998) and occurs predominantly between the ages of 30 and 50 years (Donegan and Spratt, 1995). Previous studies indicate that atypical ductal hyperplasia and atypical lobular hyperplasia are proliferative lesions with atypia and therefore have premalignant potential (Dupont et al., 2006) reported a fourfold increased risk than that of the general population for subsequent invasive carcinoma. This risk increasing to 10-fold if the patient has a first-degree relative with breast cancer. More so, studies have shown that atypical hyperplasia confers a bilateral risk for subsequent invasive carcinoma (Hartmann et al., 2005).
Sclerosing adenosis has been classified as a proliferative lesion without atypia, having a relative risk of 1.3-1.9 for invasive carcinoma (Jensen et al., 1989). This lesion accounted for 137 (7.3%) of the cases in this study. Sclerosing adenosis, a lobulocentric lesion of disordered acini, myoepithelial, and connective tissues, may be difficult to distinguish grossly from infiltrating carcinoma and may occur in association with other epithelial hyperplasia including epithelial hyperplasia and intraductal papilloma (Jensen et al., 1989). It may also coexist with invasive and in situ carcinoma (Cheng et al., 2008). A biopsy with histological diagnosis is therefore indicated in such cases.
Low-grade (benign) phylloides, a fibroepithelial tumor, accounted for 34 (1.8%) cases. In Enugu, benign phylloides accounted for 3.9% of FBDS (Anyikam et al., 2008). It is documented in the literature that benign phylloides occurs predominantly in middle-aged women between 40 and 50 years with definite rarity in childhood and adolescence in the Western countries (Juan et al., 2004).

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INFLAMMATORY AND RELATED BREAST DISEASE
Mastitis
A variety of inflammatory and reactive changes can be seen in the breast. While some of these changes are a result of infectious agents, others do not have a well-understood etiology and may represent local reaction to a systemic disease, or a localized antigen-antibody reaction, and are classified as idiopathic (Barbosa et al., 2003).
Inflammatory breast cancer, as the name suggests, mimics an infectious or inflammatory etiology. It often develops without a palpable mass lesion and is often initially misdiagnosed. In fact, most patients with inflammatory breast cancer are diagnosed after an initial treatment with antibiotics or anti-inflammatory therapies failed to show clinic improvement (Furlong et al., 1994). Mammographic and sonographic evaluations are helpful in establishing the diagnosis. Image-guided biopsy of the abnormal breast parenchyma or skin biopsy confirms the diagnosis. A negative skin biopsy should not be used to exclude the diagnosis (Irabor et al., 2008).

Acute Mastitis
Acute mastitis usually occurs during the first three months postpartum as a result of breast feeding. Also known as puerperal or lactation mastitis, this disorder is a cellulitis of the interlobular connective tissue within the mammary gland, which can result in abscess formation and septicemia. It is diagnosed based on clinical symptoms and signs indicating inflammation. (Foxman et al., 2002). Risk factors fall into two general categories: improper Cursing technique, leading to milk stasis and cracks or fissures of the nipple, which may facilitate entrance of micro-organisms through the skin; and stress and sleep deprivation, which both lower the mother’s immune status and inhibit milk flow, thus causing engorgement (Michie et al., 2003).
Because the duration of symptoms before starting treatment is found to be the only independent risk factor for abscess development, early diagnosis and early management of mastitis is of value (Michie et al., 2003). However, there is little consensus on the type or duration of antibiotic therapy and when to begin antibiotics. Because lactation mastitis is a process of subcutaneous cellulitis, detection of pathogens in breast milk nay not always be possible, so breast emptying with frequent nursing or manual pumping and beginning empiric anti-biotherapy seems to be the most appropriate approach (Barbosa et al., 2003) When puerperal mastitis-associated abscess occurs, incision and drainage are usually recommended; however, suitable patients assessed by ultrasonography can also be treated without surgery by needle aspiration and antibiotics with excellent cosmesis (Dener et al., 2003).

Granulomatous Mastitis
Granulomatous reactions resulting from an infectious etiology, foreign material, or systemic autoimmune diseases such as sarcoidosis and Wegener’s granulomatosis can involve the breast (Erhan et al., 2000). Identification of the etiology requires microbiologic and immunologic testing in addition to histopathological evaluation. Many different types of organisms can cause granulomatous mastitis (Diesing et al., 2004). Tuberculosis of the breast is a very rare disease. However, both clinical and radiological features of tuberculous mastitis are not diagnostic and easily can be confused with either breast cancer or pyogenic breast abscess by clinicians(Tavassoli et al., 2003).
Remembering the fact that traveling from one place to another in the global world has been increasing and that the prognosis for complete cure with appropriate antituberculous drug therapy is excellent, this entity should also be taken into consideration. Definitive diagnosis of the disease is based on identification of typical histological features under microscopy or detection of the tubercle bacilli with mycobacterial culture (Tewari et al., 2005). The term “idiopathic granulomatous mastitis” is used for granulomatous lesions without an identifiable cause. This diagnosis can be made only by excluding other possible causes of granulomatous lesions. An autoimmune localized response to retained and extravasated fat- and protein-rich secretions in the duct has been postulated, but the etiology of the disease remains largely unknown (Azlina et al., 2003). Histologically, chronic noncaseating granulomatous inflammation is typically limited to lobuli. The recommended therapy of idiopathic granulomatous mastitis is complete surgical excision whenever possible plus steroid therapy. Even when idiopathic granulomatous mastitis is treated appropriately, in about 50% of the cases, persistence, recurrence, and complications such as abscess formation, fistulae, and chronic are encountered, so long-term follow-up is necessary in these patients (Desing et al., 2004).

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Foreign Body Reactions
Foreign materials, such as silicone and paraffin, which are used for both breast augmentation and reconstruction after cancer surgery, may cause a foreign body-type granulomatous reaction in the breast. Silicone granulomas (“siliconomas”) usually occur after direct injection of silicone into the breast tissue or after extracapsular rupture of an implant (Van et al., 1998). Foreign body granulomatous response associated with multinucleated giant cells surround silicone(Kara et .,2000). Fibrosis and contractions may lead to clinically apparent firm nodules that may be tender.

Recurring Subareolar Abscess
Recurring subareolar abscess (Zuska’s disease) is a rare bacterial infection of the breast that is characterized by a triad of draining cutaneous fistula from the subareolar tissue; a chronic thick, pasty discharge from the nipple; and a history of multiple, recurrent mammary abscesses (Passaro et al., 1994). The disease is caused by squamous metaplasia of one or more lactiferous ducts in their passage through the nipple, probably induced by smoking (Donegan et al., 2002). Keratin plugs obstruct and dilate the proximal duct, which then becomes infected and ruptures. The inflammation eventuates in abscess formation beneath the nipple, which typically drains at the margin of the areola (Passaro et al., 1994). Abscess drainage to allow for resolution of the acute inflammation and then complete excision of the affected duct and sinus tract is successful in most cases, but abscesses may reoccur when the process develops in another duct (Rosen, 2001).
Mammary Duct Ectasia
Mammary duct ectasia, also called periductal mastitis is a distinctive clinical entity that can mimic invasive carcinoma clinically. It is a disease of primarily middle-aged to elderly parous women, who usually present with nipple discharge, a palpable subareolar mass, noncyclical mastalgia, or nipple inversion or retraction (Furlong et al., 1994). The pathogenesis and the etiology of the disease are still being debated. Smoking has been implicated as an etiologic factor in mammary duct ectasia (Rahal et al., 2005), This association appears to be more important in young women who smoke (Dixon et al., 1996). Mammary duct ectasia is usually an asymptomatic lesion and is detected mammographically because of microcalcifications. The most important histological feature of this disorder is the dilatation of major ducts in the subareolar region. These ducts contain eosinophilic, granular secretions and foamy histiocytes both within the duct epithelium and the lumen. The inspissated luminal secretions may undergo calcifications that may be the presenting sign in many patients (Sweeney et al., 1995). Mammary duct ectasia generally does not require surgery and should be managed conservatively (Sakorafas, 2001). There is no evidence in the literature indicating that mammary duct ectasia is associated with an increased risk for breast cancer. In some patients, clinical presentation and mammographic findings may suggest malignancy and biopsy may be required to exclude malignancy.

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