Rubins Textbook Questions Breast

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C: Invasive lobular carcinoma. Invasive lobular carcinoma is the second most common form of invasive breast cancer. Because the amount of fibrosis is variable, the clinical presentation of invasive lobular carcinoma varies from a discrete firm mass, similar to ductal carcinoma, to a more subtle, diffuse, indurated area. Microscopically, classic invasive lobular carcinoma consists of single strands of malignant cells infiltrating between stromal fibers, which is a feature termed "Indian filing" (see photomicrograph). Despite the innocuous cytologic characteristics of this form of invasive carcinoma, it is biologically as aggressive as the invasive ductal type. Twenty-five percent of invasive carcinomas have features of both ductal and lobular carcinoma. Lobular carcinoma in situ (choice D) is confined to the lobule. Invasive ductal carcinoma may share features of invasive lobular carcinoma, but it usually forms glands, particularly the tubular type (choice B). Diagnosis: Invasive lobular carcinoma

21 A 52-year-old woman presents with a 3-month history of a palpable breast mass. Physical examination confirms a 1-cm nodule in the upper outer quadrant of the right breast. A biopsy reveals small cuboidal cells, with round nuclei and prominent nucleoli. The cells are arranged in single cell columns, between strands of connective tissue (shown in the image). Which of the following is the appropriate diagnosis? (A) Ductal carcinoma in situ (B) Invasive ductal carcinoma, tubular type (C) Invasive lobular carcinoma (D) Lobular carcinoma in situ (E) Medullary carcinoma

C: Medullary carcinoma. Medullary carcinomas present as fleshy, bulky tumors measuring 5 to 10 cm in diameter. They are generally larger at the time they are detected than infiltrating ductal carcinomas (average size, 2 to 3 cm). This invasive tumor presents as a circumscribed mass that lacks calcifications. On gross examination, medullary carcinoma appears as a well-circumscribed, fleshy, pale gray mass. Microscopically, it is composed of sheets of cells that are highly pleomorphic and have a high mitotic index. The pathologic definition of medullary carcinoma includes a lymphoid infiltrate encompassing the periphery of the tumor. Despite the highly malignant histologic appearance of this neoplasm, it has a distinctly better prognosis than infiltrating ductal or lobular carcinoma. A dense lymphoid infiltrate is not characteristic of the other choices. Diagnosis: Medullary carcinoma of the breast

22 A 58-year-old woman has a screening mammography and is found to have a 4-cm circumscribed mass, without calcifications, in her left breast. An excisional biopsy shows solid nests and sheets of highly pleomorphic cells, with many mitotic figures, surrounded by a dense infiltrate of lymphocytes. Which of the following is the most likely diagnosis? (A) Invasive ductal carcinoma (B) Invasive lobular carcinoma (C) Medullary carcinoma (D) Paget disease (E) Phyllodes tumor

D. Paget disease Paget disease of the nipple refers to an uncommon variant of ductal carcinoma, either in situ or invasive, that extends to involve the epidermis of the nipple and areola. This condition usually comes to medical attention because of an eczematous change in the skin of the nipple and areola. Microscopically, large cells with clear cytoplasm (Paget cells) are found singly or in groups within the epidermis. The prognosis of Paget disease is related to that of the underlying ductal cancer. Eczematous change in the skin of the nipple and areola are not features of the other choices. Diagnosis: Paget disease of the breast

23 A 45-year-old woman presents with an oozing, reddish patch on her left nipple (patient shown in the image). The patient has a history of skin rashes and food allergies and believes this condition is due to an allergic reaction to her bra. Cytologic examination of fluid oozing from the skin lesion reveals neoplastic cells. Excisional biopsy shows large clear malignant cells in the epidermis of the areola. Which of the following is the most likely diagnosis? (A) Chronic dermatitis (B) Colloid carcinoma (C) Intraductal papilloma (D) Paget disease (E) Phyllodes tumor

B: Estrogen receptors Over half of breast cancers exhibit nuclear estrogen receptor protein. A slightly smaller proportion also has progesterone receptors. Women whose cancers possess hormone receptors have a longer disease-free survival and overall survival than those with early- stage cancers who are negative for these receptors. The beneficial effects of oophorectomy on survival in patients with breast cancer led to the use of estrogen antagonists in the treatment of breast cancer. In general, antiestrogen therapy seems to prolong disease-free survival, particularly in postmenopausal and node-positive women. It also lowers the risk of cancer in the contralateral breast. The latter discovery has led to the use of antiestrogens as chemoprevention in women at high risk for developing breast cancer. None of the other choices are related prognostically to breast carcinoma. Diagnosis: Invasive ductal carcinoma of the breast.

4 A 53-year-old woman discovers a lump in her breast and physical examination confirms a mass in the lower, outer quadrant of the left breast. Mammography demonstrates an ill-defined, stellate density measuring 1 cm. Needle aspiration reveals malignant ductal epithelial cells. A modified radical mastectomy is performed. The surgical specimen reveals a firm irregular mass (arrows). Which of the following cellular markers would be the most useful to evaluate before considering therapeutic options for this patient? (A) Collagenase (B) Estrogen receptors (C) Galactosyl transferase (D) Lysosomal acid hydrolases (E) Myeloperoxidase

A. BRCA1 BRCA1 is a tumor suppressor gene that has been implicated in the pathogenesis of hereditary breast and ovarian cancers. Mutations in this tumor suppres- sor gene are thought carried by 1 in 200 to 400 people in the United States. Germline point mutations and deletions in BRCA1 place a woman at a remarkable 60% to 85% lifetime risk for breast cancer. Moreover, breast cancer develops in more than half of these women before the age of 50 years. It is currently suspected that mutated BRCA1 is responsible for 20% of all cases of inherited breast cancer (about 3% of all breast cancers). Somatic mutations in BRCA1 are uncommon in sporadic (nonfamilial) breast cancers. Women with BRCA1 mutations are also at greater lifetime risk of ovarian cancer. Estrogen receptor expression (choice C) is often increased in breast cancer cells, but the gene for the estrogen receptor is not mutated. Neither estrogen receptor status nor HER2/neu expression (choice D) predict genetic predisposition. Diagnosis: Breast cancer

A 20-year-old woman asks for your advice regarding her risk of developing breast cancer. Her mother, maternal aunt, and maternal grandmother all developed breast cancer. She would like to know if she has a genetic predisposition. Laboratory tests for mutations in which of the following genes would be most likely to answer your patient's question? (A) BRCA1 (B) C-myc (C) Estrogen receptor (D) HER2/neu (E) Rb-1

D. Neutrophils The thick, yellow fluid draining from the breast fissure in this patient represents a purulent exudate. Purulent exudates and effusions are associated with pathologic conditions such as pyogenic bacterial infections, in which the predominant cell type is the segmented neutrophil (polymorphonuclear leukocyte). Mast cells (choice C) are granulated cells that contain receptors for IgE on their cell surface. They are additional cellular sources of vasoactive mediators, particularly in response to allergens. B lymphocytes (choice A) and plasma cells (choice E) are mediators of chronic inflammation and provide antigen-specific immunity to infectious diseases. Diagnosis: Acute mastitis

A 22-year-old woman nursing her newborn develops a tender erythematous area around the nipple of her left breast. A thick, yellow fluid is observed to drain from an open fissure. Examination of this breast fluid under the light microscope will most likely reveal an abundance of which of the following inflammatory cells? (A) lymphocytes (B) Eosinophils (C) Mastcells (D) Neutrophils (E) Plasma cells

E: Staphylococcus aureus. This lactating patient has developed acute mastitis. The most common organisms isolated are Staphylococcus and Streptococcus. Untreated, the infection may progress to abscess formation, which is a complication that necessitates surgical intervention. A firm, walled-off, nontender abscess may be mistaken for cancer. Acute bacterial mastitis may be treated successfully by aggressive mechanical suction, with frequent emptying of the breasts, and by the administration of antibiotics. None of the other pathogens are ordinarily seen in acute mastitis. Diagnosis: Acute mastitis

A 22-year-old woman nursing her newborn develops a tender erythematous area around the nipple of her left breast. On physical examination, a purulent exudate is observed to drain from an open fissure. Culture of this exudate will most likely grow which of the following microorganisms? (A) Candida albicans (B) Escherichia coli (C) Haemophilus influenzae (D) Lactobacillus acidophilus (E) Staphylococcus aureus

A: Acute mastitis. Acute mastitis is a bacterial infection of the breast. It may be seen at any age, but by far the most frequent setting is in the postpartum lactating or involuting breast. This disorder is usually secondary to obstruction of the duct system by inspissated secretions. The other choices are not typically associated with fever. Diagnosis: Acute mastitis

A 24-year-old woman delivers a 3.5-kg baby and begins breastfeeding her infant. The patient presents 2 weeks later with a fever of 38°C (101°F). Physical examination shows no abnormal vaginal discharge or evidence of pelvic pain but does reveal redness on the lower side of the left breast. The patient stops nursing the infant temporarily, but the symptoms per- sist, and the entire breast becomes swollen and painful. What is the most likely diagnosis? (A) Acute mastitis (B) Chronic mastitis (C) Duct ectasia (D) Granuloma tousmastitis (E) Lactating adenoma

C. The biopsy specimen shows an invasive breast cancer. Given the young age of the patient and the strong family history of breast cancer, it is reasonable to assume that she has inherited an altered gene that predisposes to breast cancer. There are two known breast cancer susceptibility genes: BRCA1 and BRCA2. Both are cancer suppressor genes. Specific c mutations of BRCA1 are common in some ethnic groups, such as Ashkenazi Jews. Estrogen receptors are expressed in 50% to 75% of breast cancers. Their presence bodes well for therapy with hormone receptor antagonists. There is no known relationship between the structure of the estrogen receptor gene and susceptibility to breast cancer. Likewise, presence of progesterone receptors in the cancer cells indicates potential response to hormonal therapy, not risk for breast cancer. HER2/neu is a growth factor receptor gene that is amplified in certain breast cancers and is a marker of poor prognosis, not susceptibility. There is alteration of TP53 in many cancers, typically acquired and not familial, including breast carcinomas, but it does not have predictive value for risk. Inheritance of RB1 mutations increases the risk for retinoblastoma and osteosarcomas, but not breast carcinomas.

A 25-year-old Jewish woman sees her physician after finding a lump in her right breast. On physical examination, a 2-cm, rm, nonmovable mass is palpated in the upper outer quadrant. No overlying skin lesions and no axillary lymphadenopathy are present. The gure shows an excisional biopsy specimen. The family history indicates that the patient's mother, maternal aunt, and maternal grandmother have had similar lesions. Her 18-year-old sister has asked a physician to determine whether she is genetically at risk of developing a similar disease. A mutated gene encoding for which of the following is most likely to be found in her sister? A HER2/neu B Estrogen receptor (ER) C BRCA1 D TP53 E Progesterone receptor (PR) F RB1

E: Rapid growth. Fibroadenomas commonly enlarge more rapidly during pregnancy and cease to grow after the menopause. Although they are hormonally responsive, a causal relationship between hormones and the pathogenesis of fibroadenoma has not been established. Development of invasive ductal carcinoma (choice A) in a fibroadenoma is rare. Diagnosis: Fibroadenoma

A 26-year-old woman presents with a breast mass that was detected on self-examination 1 week earlier. Mammography reveals a round, sharply demarcated 1-cm nodule in the right breast (shown in the image). Biopsy of the breast mass shows neoplastic epithelial ductal structures situated within a fibromyxoid stroma. The patient refuses further treatment and informs you that she wishes to become pregnant. Which of the following is the most likely effect of pregnancy on this breast lesion? (A) Development of invasive ductal carcinoma within the lesion (B) Fibrocystic change with sclerosing adenosis (C) Formation of intraductal papilloma (D) Metastasis to regional lymph nodes (E) Rapid growth

A. Fibroadenoma Fibroadenomas are common and may enlarge during pregnancy or late in each menstrual cycle. Most intraductal papillomas are smaller than 1 cm and are not influenced by hormonal changes. Lobular carcinoma in situ is typically an ill-de ned lesion without a mass effect. Medullary carcinomas tend to be large; they account for only about 1% of all breast carcinomas. Phyllodes tumors are uncommon and tend to be larger than 4 cm

A 27-year-old woman in the third trimester of her third pregnancy discovers a lump in her left breast. On physical examination, a 2-cm, discrete, freely movable mass beneath the nipple is palpable. After the birth of a term infant, the mass appears to decrease in size. The infant is breastfed without difculty. What is the most likely diagnosis? A Fibroadenoma B Intraductal papilloma C Lobular carcinoma in situ D Medullary carcinoma E Phyllodes tumor

B: Fat necrosis. A history of trauma can usually be elicited in cases of fat necrosis occurring in the breast. Initially, the lesion consists of necrosis of adipocytes and hemorrhage, after which phagocytic cells remove the lipid debris. Fibroblastic proliferation during healing leads to fingers of fibrous scar tissue that extend into the adjacent breast tissue. As a result, an irregular, fixed, hard mass may ensue and clinically resemble breast cancer. Dystrophic calcification, a common feature of breast cancer, may also be detected radiographically in areas of fat necrosis. Thus, the lesions often require biopsy to establish their benign character. The otherchoices are not associated with trauma. Diagnosis: Fat necrosis of the breast

A 30-year-old woman suffers traumatic injury to her breast while playing soccer. Physical examination reveals a 3-cm area of ecchymosis on the left breast. Two weeks later, the patient palpates a firm lump beneath the area where the bruise had been located. Which of the following is the most likely pathologic diagnosis? (A) Ductectasia (B) Fat necrosis (C) Fibrocystic change (D) Granulomatous mastitis (E) Intraductal papillomatosis

C: Fibrocystic change. Fibrocystic change of the breast refers to a constellation of morphologic features characterized by (1) cystic dilation of terminal ducts, (2) relative increase in fibrous stroma, and (3) variable proliferation of terminal duct epithelial elements. Some of the florid manifestations appear to be indicators for an increased risk for breast cancer. Such lesions are designated proliferative fibro- cystic change. Forms of fibrocystic change that do not carry an increased risk for the development of cancer, termed non- proliferative fibrocystic change, are far more prevalent. Ductal carcinoma in situ (choice A) features apparently malignant epithelial cells that have not penetrated the basement membrane. Intraductal papilloma (choice E) occurs in the subareolar lactiferous ducts. None of the remaining incorrect choices feature cystic duct dilation. Diagnosis: Fibrocystic change, proliferative

A 35-year-old nulliparous woman complains that her breasts are swollen and nodular upon palpation. A mammogram discloses foci of calcification in both breasts. A breast biopsy reveals cystic duct dilation and ductal epithelial hyperplasia without atypia (shown in the image). What is the appropriate diagnosis? (A) Ductal carcinoma in situ (B) Fibroadenoma (C) Fibrocystic change (D) Granulomatous mastitis (E) Intraductal papilloma

B: Ductal carcinoma in situ, comedocarcinoma type. Intraductal carcinoma in situ of the comedo type is composed of very large, pleomorphic cells that have abundant eosinophilic cytoplasm and irregular nuclei, commonly with prominent nucleoli, and typically grows in a solid pattern. Central necrosis is a prominent factor. The necrotic debris may undergo dystrophic calcification. On gross examination, the cut surface shows distended ducts containing pasty necrotic debris resembling comedos, hence the term comedocarcinoma. Although the malignant cells do not invade through the basement membrane of the ducts, this form of carcinoma in situ commonly incites a chronic inflammatory and fibroblastic response in the surrounding stroma. The cancer may extend within the duct system beyond the clinically detect- able tumor growth. The consequent difficulties in obtaining complete excision of the primary tumor frequently necessitate mastectomy rather than "lumpectomy." The chances of local recurrence as either in situ or invasive cancer are substantially greater in the case of the comedo subtype than the noncomedo subtype. Colloid carcinoma (choice A) features abundant mucin production. Medullary carcinoma (choice C) is composed of sheets of invasive and pleomorphic cells. Phyllodes tumor (choice D) demonstrates proliferation of spindly stromal cells. Tubular carcinoma (choice E) is an invasive well-differentiated carcinoma with well-formed small duct structures. Diagnosis: Comedocarcinoma, ductal carcinoma in situ

A 45-year-old woman discovers a solitary, freely movable mass in her right breast on self-examination, which is confirmed on physical examination. Mammography demonstrates focal calcification, with a linear configuration in the region of the breast mass. A breast biopsy (shown in the image) reveals large, pleomorphic epithelial cells confined to dilated ducts, with central zones of necrosis. What is the appropriate pathologic diagnosis? (A) Colloid carcinoma (B) Ductal carcinoma in situ, comedocarcinoma type (C) Medullary carcinoma (D) Phyllodes tumor (E) Tubular carcinoma

B: Intraductal papilloma. Intraductal papilloma is a benign breast tumor that usually causes nipple dis- charge (serous or hemorrhagic) and occurs in the lactiferous ducts of middle-aged and older women. Because intraductal papilloma is situated in the large, subareolar ducts, the lesion may be associated with a serous or bloody nipple discharge. This lesion must be distinguished from papillomatosis, which occurs in the peripheral ducts as a component of proliferative fibrocystic change. Intraductal papillomas are attached to the wall of the duct by a fibrovascular stalk. The papillomatous portion consists of a double layer of epithelial cells, an outer layer of cuboidal or columnar cells, and an inner layer of more rounded myoepithelial cells. Solitary intraductal papilloma is not a premalignant lesion or a marker for increased risk of cancer in the breast. Ductal carcinoma in situ (choice A) and lobular carcinoma in situ (choice C) feature neoplastic cells confined to ducts and lobules, respectively, and typically lack myoepithelial cells. Paget disease (choice E) is a form of carcinoma that involves the epidermis of the nipple and areola. Diagnosis: Intraductal papilloma

A 54-year-old woman complains of bloody discharge from her left nipple. Physical examination reveals a 0.5-cm nodule in the subareolar breast tissue, which is surgically excised. Histologic examination (shown in the image) reveals cuboidal and myoepithelial cell-lined vascular connective tissue cores, which project into the lumen of a major lactiferous duct. Which of the following is the appropriate diagnosis? (A) Ductal carcinoma in situ (B) Intraductal papilloma (C) Lobular carcinoma in situ (D) Medullary carcinoma (E) Paget disease

A. Gene amplification Overexpression of HER2/ neu is identified in 10% to 35% of primary breast tumors and is mostly attributable to gene amplification. Amplification or overexpression of HER2/neu has also been described in cancers of the lung, ovary, and stomach. Overexpression can be determined by immunohistologic detection of the c-erbB2 protein on the cell membrane or by analysis of the HER2/neu gene using fluorescent in situ hybridization. Patients whose tumors demonstrate HER2 gene amplification benefit from therapy with a monoclonal antibody (Herceptin) that selectively binds to the extracellular domain of the protein. Although the other genetic processes occur in some cancers, they are unrelated to HER2/neu expression. Diagnosis: Breast cancer

A 54-year-old woman presents with a mass in her right breast that she first palpated 5 days before. A breast biopsy reveals malignant cells, and a mastectomy is performed. Immunohistochemical staining is performed for HER2/neu (shown in the image). Which of the following genetic mechanisms best accounts for the intensity of staining in this specimen? (A) Gene amplification (B) Insertional mutagenesis (C) Chromosomal nonhomologous crossing over (D) Polyploidy (E) Single nucleotide polymorphism

B: Invasive ductal carcinoma Cancer in the male breast is uncommon and accounts for less than 1% of all cases of breast cancer. The most common subtype is infiltrating (invasive) ductal carcinoma. Because there is less fat in the male breast, invasion of chest wall muscles is more frequent at the time of diagnosis. For tumors of the same stage, however, the prognosis for male breast cancer is similar to that of female breast cancer. Choice A is a skin tumor and the other choices (C, D, and E) are rare in the male breast. Diagnosis: Male breast cancer, invasive ductal carcinoma of the breast

A 55-year-old man presents with a solitary breast mass and biopsy reveals malignant cells. Immunohistochemical staining experiments show that the tumor cells are positive for HER2/ neu and cytokeratins 4 and 11 and negative for estrogen recep- tors. What is the most likely diagnosis? (A) Basal cell carcinoma (B) Invasive ductal carcinoma (C) Invasive lobular carcinoma (D) Medullary carcinoma (E) Tubular adenoma

B: Lobular carcinoma in situ. Lobular carcinoma in situ arises in the terminal duct lobular unit. Malignant cells appear as solid clusters that pack and distend the terminal ducts but not to the extent of ductal carcinoma in situ. The lesion does not usually incite the dense fibrosis and chronic inflammation so characteristic of intraductal carcinoma in situ and is, therefore, less likely to cause a detectable mass. It is not uncommon for lobular carcinoma in situ to be an "incidental" finding in a biopsy that was prompted by benign changes. As with intraductal carcinoma in situ, 20% to 30% of women with lobular carcinoma in situ receiving no further treatment after biopsy will develop invasive cancer within 20 years of diagnosis. However, about half of these invasive cancers will arise in the contralateral breast and may be either lobular or ductal cancers. Thus, lobular carcinoma in situ, more than ductal carcinoma in situ, serves as a marker for an enhanced risk of subsequent invasive cancer in both breasts. The histologic appearance is not consistent with any of the other choices. Diagnosis: Lobular carcinoma in situ

A 58-year-old woman presents with an irregular nodularity that has developed in her right breast over the past 3 months. Mammography demonstrates irregular densities in both breasts. A needle biopsy of one breast lesion is shown. An excisional biopsy of the contralateral breast shows similar histology. Which of the following is the most likely pathologic diagnosis? (A) Colloid carcinoma (B) Lobular carcinoma in situ (C) Malignant phyllodes tumor (D) Medullary carcinoma (E) Tubular carcinoma

B: Cirrhosis. Gynecomastia refers to an enlargement of the adult male breast and is morphologically similar to juvenile hypertrophy of the female breast. In the adult man, gynecomastia is caused by an absolute increase in circulating estrogens or by a relative increase in the estrogen/ androgen ratio. Gynecomastia associated with excess estrogens occurs with (1) the intake of exogenous estrogens, (2) the presence of hormone-secreting adrenal or testicular tumors, (3) the paraneoplastic production of gonadotropins by cancers, and (4) metabolic disorders, such as liver disease and hyperthyroidism, which are characterized by increased con- version of androstenedione into estrogens. Gynecomastia is often idiopathic, in which case it is commonly unilateral. The other choices are not associated with gynecomastia. Diagnosis: Gynecomastia

A 60-year-old man presents with painless, bilateral enlargement of both breasts. The patient has a history of nodular prostatic hyperplasia and is taking medication for hypercholesterolemia. Physical examination reveals no discrete breast masses or axillary lymph node enlargement. Which of the following is the most likely underlying cause of breast enlargement in this patient? (A) Chronic glomerulonephritis (B) Cirrhosis (C) Non seminomatous germ cell neoplasm (D) Parathyroid adenoma (E) Progressive systemic sclerosis

D: Phyllodes tumor. Phyllodes tumor of the breast is a proliferation of stromal elements accompanied by a benign growth of ductal structures. These tumors usually occur in women between 30 and 70 years of age. Phyllodes tumors resemble fibroadenomas in their overall architecture and the presence of glandular and stromal elements. Like fibroadenoma, benign phyllodes tumor is sharply circumscribed, and the cut surface is firm, glistening, and grayish white. Microscopically, the stroma of a benign phyllodes tumor is hypercellular and has mitotic activity. The distinction from fibroadenoma is made not on the size, but on the histologic and cytologic characteristics of the stromal component. Malignant phyllodes tumors have an obviously sarcomatous stroma with abundant mitotic activity, and the stromal component is increased out of proportion to the benign duct elements. They are usually poorly circumscribed, with invasion into the surrounding breast tissue. Sarcomatous elements are not features of the other choices. Diagnosis: Phyllodes tumor of the breast

A 60-year-old woman presents with a large breast mass that she first detected 3 months ago. Mammography reveals a well- circumscribed mass measuring 8 cm in diameter. A breast biopsy shows loose fibroconnective tissue with a sarcomatous stroma, abundant mitoses, and nodules and ridges lined by cuboidal epithelial cells. Which of the following is the appropriate diagnosis? (A) Fibroadenoma (B) Medullary carcinoma (C) Paget disease (D) Phyllodes tumor

A. Colloid carcinoma Colloid (mucinous) carcinoma is an invasive variant that tends to occur in older women. On cut section colloid carcinoma has a glistening surface and mucoid consistency. Histologically, it is composed of small clusters of epithelial cells, occasionally forming glands, floating in pools of extracellular mucin. In its pure form, colloid carcinoma has a considerably better prognosis than infiltrating ductal or lobular carcinoma. However, it is often admixed with infiltrating ductal carcinoma, in which circumstance the prognosis is determined by the ductal component. Abundant mucin production is not a feature of the other choices. Diagnosis: Mucinous carcinoma of the breast

A 65-year-old woman presents with a palpable breast mass that she palpated 1 month earlier. Physical examination reveals a soft, jelly-like tumor measuring 5 cm in diameter. Histologic examination of a breast biopsy is shown in the image. What is the appropriate diagnosis? (A) Colloid carcinoma (B) Lobular carcinoma (C) Medullary carcinoma (D) Paget disease (E) Phyllodes tumor

D: Women of reproductive age. Fibrocystic change is most often diagnosed in women from their late 20s to the time of menopause, and some fibrocystic change occurs in 75% of adult women in the United States. The morphologic hallmarks of nonproliferative fibrocystic change seen in this patient are an increase in fibrous stroma and cystic dilation of the terminal ducts. Fibrocystic change occurs in multiple areas of both breasts. A dominant cyst or aggregate of fibrous connective tissue containing smaller cysts may manifest as a discrete mass, prompting biopsy to exclude the possibility of cancer. The large cysts often contain dark fluid that imparts a blue color—the so-called "blue-domed cysts of Bloodgood." Aspiration of a large cyst will usually cause it to collapse and the mass to disappear. A frequent concomitant of nonproliferative fibrocystic change is an alteration of the epithelial lining, termed apocrine metaplasia. The metaplastic cells are larger and more eosinophilic than the cells that usually line the ducts and resemble apocrine sweat gland epithelium. The frequency of fibrocystic change decreases progressively after menopause (choice B). Fibrocystic change is not encountered during puberty (choice C). Oral contraceptives (choice E) do not increase the frequency of fibrocystic change. Diagnosis: Fibrocystic change, nonproliferative

A woman consults her physician because of painful swelling of her breasts. Physical examination reveals nodularity of both breasts. Mammography shows irregular areas of increased density in the lower, outer quadrants of both breasts. A breast biopsy reveals increased fibrous stoma, cystic dilation of the terminal ducts, and varying degrees of apocrine metaplasia. This patient's condition is most commonly seen in which of the following groups? (A) Patients with testicular feminization syndrome (B) Postmenopausal women (C) Pubertal girls (D) Women of reproductive age (E) Women treated with oral contraceptives

E. Status of the axillary lymph nodes Although all of the choices are prognostic indicators for breast cancer, the most important prognostic factor at the time of diagnosis is stage. A sentinel node assessment often is performed intra- operatively to assess the status of the ipsilateral lymph nodes. The sentinel lymph node is the most proximate lymph node and is assumed to be the initial site of nodal metastasis. It is identified with a dye or radioactive material. An axillary lymph node dissection is performed if metastatic tumor is identified in the sentinel lymph node. The presence of invasion indicates that tumor cells have access to lymphatic and blood vascular channels in the stroma, increasing the possibility of metastases to regional lymph nodes and distant sites. The prognosis for women with distant metastases (stage IV) is poor in terms of survival, but palliative treatment may significantly prolong life. With the expanding use of screening mammography, more than half of the breast cancers currently diagnosed in the United States manifest as stage I disease, and almost all of these women will be cured by surgery. Diagnosis: Invasive ductal carcinoma of the breast

Upon self-examination, a 53-year-old woman discovers a lump in her left breast. Physical examination reveals a palpable lump about 1 cm in diameter in the outer quadrant of the left breast. No palpable lymph nodes are found in the axilla. Mammography reveals an ill-defined, stellate density measuring 1 cm in the left breast. Fine-needle aspiration of the mass discloses malignant epithelial cells. A partial mastectomy is performed and shows invasive ductal adenocarcinoma. Which of the following is the most important prognostic factor for this patient? (A) Estrogen receptor status of the tumor tissue (B) Histologic grade of the tumor (C) Inherited BRCA1 gene mutation (D) Somatic mutation of the p53 tumor suppressor gene (E) Status of the axillary lymph nodes


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