Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Neoplasia of the Male Breast
Introduction
The male breast is different in many respects from the female breast, in terms of both composition and pathology. Malignant conditions may occur, albeit far less commonly than seen in females, with advanced molecular studies suggesting that these conditions are different from female breast cancers (FBCs). The resulting implications for patient management are being increasingly recognized, with recent clinical studies specifically designed for understanding and treating male breast cancer (MBC).
Embryogenesis and Puberty
The in utero development of the male breast is similar to that of the female breast with equivalent components of ectoderm- and mesoderm-derived epithelia (luminal and myoepithelial cells) and stroma (intralobular and interlobular fibrovascular tissue), with the major difference being greater numbers of lobules in the female breast. The sensitivity of fetal breast tissue to maternal hormones results in variable glandular complexities, including secretory change, that is common in both male and female newborns. At birth the ductal system opens onto the surface through the breast pit on the skin surface, with formation of the nipple and areolar complex occurring after birth as the skin surrounding the breast pit proliferates. The breast then remains the same with little change in both sexes until the onset of puberty.
During puberty, the threefold increase in circulating estrogens in males causes the ductal and periductal mesenchymal breast tissue to undergo proliferation with breast enlargement. However, there is subsequent involution of these structures caused by rising testicular androgen levels that increase up to adult levels, which are approximately 15 to 30 times higher than baseline prepubertal concentrations. In comparison with the female adult breast, the male breast shows an absence of Cooper ligaments and has fewer terminal ductal lobular units (TDLUs), an involuted ductal system, less prominent breast stroma, and more prominent pectoralis musculature.
Benign Proliferative Lesions
Fibrocystic Change
Unlike the female breast, very few cases of fibrocystic change (FCC) are noted in the male breast, most likely due to the absence of cycling of estrogen and progesterone that is seen in premenopausal women. In a series of 164 male breasts imaged for clinical disease, only two patients (1.2%) had FCC. Most other cases of FCC are isolated reports, with one male breast showing FCC in conjunction with a papilloma and an intracystic papillary carcinoma, and a second case report of FCC occurring with papillary hyperplasia and presenting as a freely mobile breast mass in a healthy male. FCC is not associated with increased risk of cancers in males ( Fig. 32.1 ).
Sclerosing Adenosis
Sclerosing adenosis, either as a part of FCC or alone, is a distinct proliferative lesion seldom seen in males due to a physiological lack of lobular development and absence of the premenopausal female hormonal milieu. There have only been rare case reports in males, with one case of co-occurrence with multiple papillomas and another as an incidental post mortem finding in a 41-year-old male with disseminated small cell carcinoma, secondary to ectopic hormone production.
Juvenile Papillomatosis
Juvenile papillomatosis is a benign focal proliferative lesion of the breast characterized by numerous cystic spaces with combinations of ductal papillomatosis, epithelial hyperplasia, apocrine metaplasia, sclerosing adenosis, cyst formation, and duct stasis ( Fig. 32.2 ) that is almost exclusively described in females younger than 30 years. There is a strong association with family history of breast cancer (reported in 33% to 58% of cases), with 4% to 15% of cases showing concurrent carcinoma at presentation and a 10% incidence noted in a study of 41 women after 14 years of follow up. Juvenile papillomatosis of the male breast is exceedingly rare, with only 11 cases reported in the literature to date. Of these, four patients were younger than 2 years, and the remaining patients were between 11 and 33 years of age. Because of the rarity of its occurrence, an association with familial breast cancer was not noted, with only two cases of MBC reported in a 33-year-old and a 45-year-old. Interestingly, in the four cases younger than 2 years, two patients manifested with strong signs of Noonan syndrome of NF1 (multiple café-au-lait spots), and one had a possible overlapping syndrome (Neurofibromatosis-Noonan syndrome), suggesting the molecular pathways modulating cell proliferation and tumorigenesis in NF1 may be significant in male juvenile papillomatosis. This association has not been documented in females.
Benign Papillary Lesions
Intraductal Papilloma
Intraductal papilloma is a common lesion encountered in the male breast and sometimes coexisting with MBC, although it is not a known risk factor for MBC. Clinically, papilloma in men presents similarly to papilloma in women, with common symptoms and signs including serous to bloody nipple discharge and presentation as a breast mass. Patient age at presentation ranges from 3 months to 82 years. Etiological factors may include increased serum prolactin levels with cases noted in patients receiving long-term phenothiazine therapy.
Radiological changes are the same as those is seen in females, and papillomata can be detected on mammography, ultrasound, galactography, or magnetic resonance imaging (MRI). Macroscopically, papilloma often have a cystic and solid component and generally range in size from 2 to 30 mm with rare instances of lesions measuring more than 50 mm. Microscopic findings include fronds composed of fibrovascular cores lined by proliferating ductal epithelium and myoepithelial cells (MECs) in an orderly polarized fashion. The epithelium is composed of cuboidal to columnar cells with mild pleomorphism, nuclear hyperchromasia, and only scattered mitotic figures ( Fig. 32.3 ). Foci of apocrine metaplasia and numerous psammoma bodies may also be seen. Although most papillomas are usually solitary, rare instances of multiple papillomata have also been reported in male patients. This is a different process from juvenile papillomatosis (see previous section). Because papillary carcinomas in the male breast are not insignificant, the management recommendation for these lesions has been for investigation and excision to exclude invasive carcinoma, with a few instances of atypical proliferative lesions such as atypical ductal hyperplasia (ADH) having been identified in male papilloma. Most patients are treated with local excision, with mastectomy performed occasionally. Rare recurrences have been reported but are successfully treated with reexcision.
Florid Papillomatosis/Nipple Duct Adenoma
Also called adenoma of the nipple, florid papillomatosis of the nipple, is an uncommon entity seen within the male breast with only 14 cases of these benign lesions reported in the literature to date. The most common presenting symptoms are subareolar nodule formation and erosion of the nipple. Nipple discharge, tenderness, and erythema have also been reported with some cases clinically mimicking and initially diagnosed as Paget’s disease of the breast.
The prominent histological feature is ductal proliferation with associated fibrosis forming a mass with a pseudoinvasive pattern. Ducts may show florid papillary hyperplasia that may entirely replace the nipple stroma and distort and obscure the underlying ductal pattern. The presence of MECs lining ducts should be identifiable but may be obscured partially or be attenuated because of marked ductal proliferation or ductal fibrosis. Notably, rare examples of coincidental breast carcinoma have been reported in males. Resection of the nipple and the subareolar tissue is an appropriate treatment in most cases of nipple adenoma. Complete excision of the nipple and areola with an underlying wedge of breast is reserved for patients with larger lesions. Recurrences are rarely reported after adequate excision.
Fibroepithelial Lesions
Fibroadenoma
Although very common in females, fibroadenoma is an uncommon benign lesion in males. The pathobiology of the development of fibroadenoma in males is still unknown, and it is suggested that some lesions may represent poorly developed foci of gynecomastia. There are reports of fibroadenomas occurring in males receiving estrogen therapy and in patients following treatment with methyldopa, chlordiazepoxide, and spironolactone. A case of fibroadenoma associated with rectal adenocarcinoma and polyposis coli has also been described. As in females, these lesions are well circumscribed, relatively mobile in situ, and have a gray-white color, with a whorled cut surface and numerous slits on the cut surface ( Fig. 32.4 ). Most are smaller than 3 cm, although one case of a giant fibroadenoma up to 25 cm has been reported in a 72-year-old man receiving antiandrogen prostate cancer therapy. Histologically, there is a combination of proliferation of ductal epithelium surrounded by fibrous stroma. Two main patterns are seen: intracanalicular (characterized by more prominent stromal proliferation resulting in compressed slit-like ducts) and pericanalicular (characterized by stromal proliferation around ducts with more open round or oval ducts).
Mammary Hamartoma
Breast hamartomas are well-circumscribed, distinct lesions histologically characterized by lobular aggregates of disorganized but mature breast tissue elements including epithelium admixed with fat, smooth muscle, and stroma. Radiologically, these lesions can have morphological features overlapping with fibroadenomas and pseudoangiomatous stromal hyperplasia (PASH). Rare case reports of mammary hamartomas have been reported in males and are almost invariably initially misdiagnosed as gynecomastia. The macroscopic and histological features are identical to those seen in females.
Phyllodes Tumor
Several cases of phyllodes tumors have been reported in males, including a case of a phyllodes tumor arising in anogenital mammary-like glands in a 41-year-old man. The etiology is unknown, although some have postulated excess estrogen as a causative factor for development of these tumors in men as gynecomastia is often observed in the background breast; one case arose in a male 9 years after radiotherapy. The tumors present as a painless mass and sizes range from 1 to 30 cm. Histologically, the tumor demonstrates a typical leaf-like architecture with stromal hypercellularity and mild to moderate cytological atypia. Grading has used female criteria, and of the 19 cases reported in detail in the literature, 10 were classified as benign phyllodes tumors, two as a borderline lesion, and seven as malignant. Most of these tumors were treated by wide excision, and to date, two cases of recurrent malignant phyllodes tumor have been noted, with one case of disease progression in a 73-year-old man showing local and pulmonary recurrence 3 months after excision of a 26-cm tumor, with subsequent death 1 month later.
Gynecomastia
Clinical Presentation
Gynecomastia is a common benign condition that can occur in males of all ages with three discrete age peaks: within neonates, during puberty, and in adults 50 to 80 years of age. The condition itself is loosely defined as the diffuse or focal proliferation of male glandular tissue often resulting in a painful retroareolar mass. Prevalence is estimated to be between 30% and 64% depending on clinical and histological interpretation.
Although pathogenesis is not completely understood, gynecomastia is thought to occur due to an increase in the effect of estrogen relative to androgen, with etiology varying among the three age peaks. In neonatal gynecomastia, the in utero action of maternal and placental estrogens is significant, whereas most pubertal gynecomastia (most commonly seen in 13- to 14-year-olds) is due to normal physiological hormonal changes. In addition to idiopathic causes in prepubertal and adult patients, there are often secondary pathological processes. These secondary processes either result in elevated serum estrogen (most commonly due to extragonadal conversion of androgens to estrogens by tissue aromatases and linked to obesity; estrogen-secreting neoplasms; adrenocortical lesions; and hCG-producing tumors) or are due to decreased free serum testosterone arising from gonadal failure (as seen in Klinefelter syndrome, mumps orchitis, or secondary to hypothalamic and pituitary disease). Gynecomastia is also noted to occur with malnutrition, hyperthyroidism, chronic liver disease, and androgen resistance syndromes. Up to 25% of adult gynecomastia is thought to be drug induced, and is broadly categorized depending on the type of drug action: type 1 drugs (digitalis, diethylstilbestrol) that are estrogenic, type 2 drugs (clomiphene, gonadotrophins) that enhance endogenous estrogen production, and type 3 drugs (ketoconazole, metronidazole, Zoladex), which inhibit testosterone synthesis and action. The majority of gynecomastia occurs bilaterally, with clinical examination showing palpable retroareolar and even axillary glandular tissue which is tender to touch. The tissue quality changes over time, with an increasing firmness present in gynecomastia of longer than 2 to 3 years’ duration.
Clinical Imaging
A combination of mammography and ultrasound is often used, with good sensitivity and specificity, in the diagnosis of gynecomastia. There are three mammographic patterns: nodular (usually appearing as a spherical funnel–shaped subareolar or outer-quadrant mass radiating from the nipple and fused with surrounding fatty tissue); dendritic (most often retroareolar with a classic flame- or fan-shaped configuration extending radially, which correlates with increasing histological fibrosis, and consistent with a duration of months to years ); and diffuse (resembling dense fibroglandular tissue in the female breast with radial extension into deep fatty tissue, representing a chronic fibrotic stage of disease).
Gross Pathology and Microscopy
The macroscopic appearance of gynecomastia may range from a soft rubbery to firm gray or white tissue that forms a discrete mass or an ill-defined area of induration. Two disrinct patterns of histological changes are seen in gynecomastia. The so-called florid type (type 1) is characterized by periductal cuffing, marked ductal epithelial hyperplasia, and mitotic activity. Concomitant myoepithelial hyperplasia may also be seen. Features of atypia encountered in the florid type may include cribriform and papillary patterns of hyperplasia. In the fibrous-type pattern (type 2), there is minimal epithelial proliferation and the stroma is denser and collagenized ( Fig. 32.5 ). Apocrine metaplasia and squamous metaplasia can be seen ( Fig. 32.6 ). Variations in stroma may show identical to female PASH.
The two phases (florid and fibrous) were originally thought by Nicolis and coworkers to represent temporal progression with an initial proliferative epithelial phase in the first year followed by the onset of a fibrous nonproliferative phase from 6 months onward. However, a large study of more than 100 cases of gynecomastia by Page and Ramos showed no correlation between pattern, age of patient, and duration of lesion. Interestingly, a correlation between estrogen stimulation and florid-type pattern is seen with histology also varying according to the etiology and type of estrogenic stimulation. Thus, gynecomastia associated with Klinefelter syndrome shows dense hyalinized stroma with few ducts in comparison with the marked ductal epithelial proliferation encountered in conditions with excess estrogen administration.
Immunohistochemically, the ductal epithelium in gynecomastia appears to be composed of three layers: inner most a luminal layer of smaller cells is present showing expression of CK5/6 and CK14 with negative expression of estrogen, progesterone, and Bcl-2 (an estrogen receptor (ER)–regulated marker) Bcl-2. An intermediate luminal layer of tall cuboidal and columnar cells show positive expression for hormone receptors (HR) and Bcl-2, and an outer-most myoepithelial layer is correspondingly positive for basal cytokeratins (CKs). In comparison, the normal male breast only contains a single layer of HR+ and Bcl-2+ luminal cells and a deeper myoepithelial layer ( Fig. 32.7 ).
Fine-needle aspiration cytology (FNAC) and/or core biopsy have been shown by many studies to be reliable tools for diagnosing male breast lesions, with a diagnostic accuracy of close to 100% for gynecomastia. The cytological features of gynecomastia that are seen include mild to moderately atypical cells ductal type cells, with overall mild to moderate cellularity, cohesive sheets of bland cells, and bipolar bare nuclei.
While gynecomastia is not a risk factor for MBC, premalignant and malignant changes may be seen, albeit rarely, with the largest series showing ADH in 0.4% to 2.0%, in situ carcinoma in 0.18%, and carcinoma in 0.11% to 0.22% in adult gynecomastia.
Management
Invariably, all neonatal and pubertal cases of gynecomastia are physiological and self-limiting, with spontaneous resolution seen in almost all cases within 24 months of onset. All adult and persistent pubertal gynecomastia should be investigated with management individualized with a focus on confirming diagnosis and excluding malignancy, and identifying and treating any underlying causes. Because most cases will undergo some form of regression, there are no guidelines determining whether or when medical intervention should occur. In cases where a clear underlying medical condition or medication is suggested to be causative, such as in hyperthyroidism or alcoholic liver disease, the treatment of the underlying condition often results in regression of the disease.
Clinical examination should include bilateral breast and axillary assessment as well as examination of the testis for signs of primary tumor, neurological examination for pituitary disorders, and examination for clinical thyroid disease. Blood tests may include renal and liver function tests, pituitary hormones (prolactin, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), sex hormones (testosterone and estradiol), and germ cell tumor markers (beta-human chorionic gonadotropin [β-hCG], alpha fetoprotein, and lactate dehydrogenase [LDH]). In clinically suspicious lesions, further imaging may be used, with mammography being particularly useful in excluding pseudogynecomastia, which is the accumulation of fatty tissue only, with no glandular component, and MBC.
Because gynecomastia is usually caused by an imbalance of androgenic and estrogenic effects on the breast, medical therapies including antiestrogens, androgens, and aromatase inhibitors (AIs), in particular tamoxifen, raloxifene, and clomiphene citrate, have been investigated as potential treatment options. These have been generally well tolerated with partial to complete response rates of 36% to 95%. Androgen therapy has shown some effect over placebo (complete response rate: 23% vs. 12%) and is recommended in cases where testosterone deficiency is present. The data on treatment with AIs are less convincing, with only case studies to date showing a treatment response and larger studies showing no greater efficacy than placebo. Nevertheless, antiestrogens and AIs may be useful in short-term management of gynecomastia-associated mastalgia, and in cases where surgery may not be possible.
Surgery is useful in the management of patients with long-standing symptomatic gynecomastia or when medical therapy is not appropriate or successful. Several clinical classification systems have been devised based on the volume of the gynecomastia/breast size, skin redundancy, tissue predominance, breast ptosis, breast tuberosity, nipple malposition, chest shape, breast skin elasticity, upper abdominal laxity, and absence of sternal notch, to guide surgical management with treatment options ranging from liposuction to nipple-sparing subcutaneous mastectomies, including newer endoscopic techniques. In a small series of adult gynecomastia, long-term follow-up of up to 13.8 years showed a 37.5% rate of recurrence, with a higher rate in patients who initially presented with gynecomastia with a prominent fat component (62.5%).
Differential Diagnosis
The two main differential diagnoses are pseudogynecomastia/lipomastia (which is seen in older men and overweight men), and MBC. Smaller lesions that may mimic gynecomastia also include lipomas and fat necrosis.
Key Clinical Points
Gynecomastia
-
Three clinical types: neonatal, pubertal, and adult.
-
Neonatal and pubertal types usually resolve within 24 months of onset and may be managed with reassurance and watchful waiting.
-
Further investigation is recommended for persistent pubertal and adult gynecomastia to determine underlying etiology.
-
Management should be individualized and may include medical and surgical interventions and psychological support.
-
Surgery may be offered in cases of long-term gynecomastia and/or with failure of medical therapy.
Key Clinical Imaging Features
Key Pathological Features
Gynecomastia
-
Florid phase characterized by periductal cuffing, marked ductal epithelial hyperplasia, and mitotic activity.
-
Stromal proliferation, often similar to pseudoangiomatous stromal hyperplasia, is common and is sometimes the only proliferative cellular change.
-
Needle aspiration cytology has high specificity for gynecomastia.
Other Benign Disorders of the Male Breast
Several inflammatory disorders have been described in the male breast that may present as a breast mass. There have been reports of subareolar breast abscess presenting with an acute onset of swelling, with a case of bilateral abscess in a 38-year-old man and cases of parasitic infection. Treatment consisted of excision, drainage, and antimicrobials. A case of Zuska disease (a fistula from the areolar skin to a lactiferous duct) has also been described within the male breast and has been successfully treated with complete excision of the fistula and no evidence of disease recurrence. A case of subcutaneous panniculitis and vasculitis has also been reported in a 54-year-old male who presented with a hard, painful right breast nodule.
Soft tissue lesions may also present as a localized mass and may mimic MBC. Although still rare, the most commonly seen is myofibroblastoma, which is more common in males than females (ratio 2:1 to 4:1), with a predominance for the sixth and seventh decades. Grossly, they are nodular with a firm pink-tan whorled cut surface. Although they are usually smaller than 3 cm in size, rare giant myofibroblastomas up to 15 cm in size and weighing over 2 kg have been reported. Histologically, myofibroblastomas are well-circumscribed but unencapsulated tumors with uniform, bland spindled cells arranged in short fascicles separated by thick hyalinized collagen bundles and with intermixed adipose tissue. The spindle cells have eosinophilic to amphophilic cytoplasm with poorly defined borders. Nuclei are oval to tapered with a fine chromatin pattern and small nucleoli. Mitotic activity is low (<2 per 10 high-power fields [HPFs]), with no atypical mitoses; however, nuclear atypia with multinucleation can be focally present. Mast cells are frequently seen and breast ducts and lobules are absent. As in the female, variations include the cellular, epithelioid (>50% of cells are epithelioid), myxoid, and lipomatous variants (>75% of the tumor contains fatty tissue). Immunohistochemistry (IHC) is often required to confirm diagnosis and exclude the main differential diagnoses, which include metaplastic breast carcinoma, myoepithelioma, spindle cell lipoma, solitary fibrous tumor, and low-grade myofibroblastic sarcoma. Myofibroblastomas are characteristically positive for CD34, vimentin, and desmin, with variable expression of ER, progesterone receptors (PgR), androgen receptors (AR), smooth muscle actin (SMA), calponin, and caldesmon, and rare expression of CD10 and CD99. A CK panel should be used to exclude metaplastic carcinoma (i.e., CK5, CK14, CK18, and AEI/3), and S100 should separate melanotic, lipomatous, and nerve sheath soft tissue lesions. Treatment is surgical excision, with no reported cases of recurrence or spread noted in males and only one case of recurrence in a female.
Other rare benign soft tissue lesions reported in the male breast include granular cell tumor, angioleiomyoma, neurofibroma, fibromatosis, nodular fasciitis, lipoma, leiomyoma, hemangiopericytoma, glomus tumors, and hemangiomas, with similar histological appearance and behavior to lesions seen in female breasts.
Carcinoma of the Male Breast
The incidence of MBC rose 40% from 1975 to 2015, an increase exceeding that of FBC by 25%. In 2015, MBC had an estimated worldwide prevalence in the general population of approximately 1.26 to 1.28 per 100,000. Similar to FBC, there appears to be regional and ethnic variation, with the lowest rates of incidence seen in Asian men and higher rates seen in men living in West Africa and in Black men compared with White men. The highest incidences are reported in Jewish men, due to a genetic predisposition for breast cancer. The American Cancer Society estimated that in 2019, 2,670 new cases of MBC would be diagnosed in the United States, with an 18% mortality. Unlike the bimodal distribution of FBC, MBC shows a gradual cumulative increase in incidence with age, with no early-onset breast cancers. There are conflicting data as to whether MBC has a worse mortality rate than FBC (HR 1.15–1.19, p <0.001) with some studies showing no difference with FBC after correcting for stage, treatment, age, and comorbities. Nevertheless, younger women and older men appear to suffer poorer survival when compared with their opposite age–related cohorts.
The overall 5-year survival rate in males with breast cancer appears to have marginally improved from 73% (94) to 82.8% from 2004 to 2014. More recent studies of MBCs are beginning to reveal increasing differences with FBC, with the American Society of Clinical Oncology (ASCO) expert committee recently publishing specific guidelines for the management of MBC.
Risk Factors
Germline Predisposition
Population-based studies show that up to 33% of MBCs may arise within a background of familial breast and ovarian cancer, intimating that germline susceptibility is a significant risk factor. The highest mutation frequencies (50%–100%) are noted in males with three or more breast/ovarian cancers in first-degree relatives. Of these, up to one-third arise in BRAC1/2 mutation carriers (0%–4% of all MBCs for BRAC1 and 4%–16% for BRAC2), with the remainder due to other unknown underlying genetic mechanisms. BRAC1 and BRAC2 are a class of tumor suppressor genes that have a key role in DNA repair and cell cycle control, with mutations of these genes having been linked to hereditary breast, prostate, and pancreatic cancers. A low threshold for germline testing has been recognized for MBCs, with the ASCO guidelines recommending germline testing for all confirmed cases.
BRAC2
Perhaps the best characterized and studied predisposition gene in MBCs is BRAC2. It is one of the strongest known risk factors for MBC, with a risk ratio of 80 to 100 times that of the general male population. It also carries a lifetime risk of breast cancer in male carriers of 7% to 10%, which is similar to the overall breast cancer risk in many female populations. BRAC2 appears to also be a significant driver of sporadic nonfamilial MBCs with frequent somatic alterations of BRAC2. BRAC2 gene polymorphism, such as the N372H variant, also shows a significant increased risk of MBC in homozygous male carriers younger than 60 years (odds ratio [OR], 5.6). BRAC2 abnormalities in MBCs are mainly point mutations in contrast to BRAC1 abnormalities in which large genomic rearrangements are quite common. And although cancer-specific cluster regions in BRAC2 have been noted for other cancers (e.g., the ovarian cancer–specific cluster region [OCCR] within exon 11), MBC-specific regions have not been identified. There is, however, an increased frequency of carriers with truncating BRAC2 mutation in familial MBCs compared with BRAC2 FBCs.
MBCs arising in BRAC2 mutation carriers appear to contain particular characteristics. They are usually of a higher grade (OR 2.98 and 5.53 for grades 2 and 3) compared with sporadic MBCs, and are more frequently lymph node positive (OR 1.37). Although most are invasive carcinomas of no special type (IC-NSTs), overrepresentation of invasive micropapillary carcinomas is seen. Immunophenotypically, there is also an association with increased frequency of the human epidermal growth factor receptor 2 (HER2) intrinsic phenotype. BRAC2 MBCs show a higher grade ( p = 0.005) and are more likely to be ER+ and PgR+ (OR 10.59 and OR 5.04. respectively) compared with BRAC2 FBCs. Male BRAC2 carriers with breast cancer also have a risk of prostate cancer above the normal general male population and male BRAC2 carriers without breast cancer.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
