20 - 114: PAGET'S DISEASE

Question 1

Which of the following is an INCORRECT statement?

a. Paget’s disease most commonly affects the unilateral nipple/areola while EMPD most commonly affects the vulva, perianal skin, scrotum, and penis
b. Paget’s disease peak at 50-60 years old while EMPD peak at 60-80 years old
c. In contrast to Paget’s disease, most cases of EMPD disease are not associated with an underlying adnexal carcinoma or visceral malignancy
d. In contrast to EMPD, In rare cases, ectopic Paget’s disease has been reported in areas that are relatively free of apocrine glands, such as the chest, abdomen and thigh
e. All statements are correct

Answer 1

Answer: D.

Question 2

EMPD of the external male and female genitalia may be associated with tumors of which two organs?

a. colon and rectum
b. testes and cervix, respectively
c. ureters and kidneys
d. urethra and bladder

Answer 2

Answer: D. pp. 1935

Question 3

The most commonly reported symptom/s in both Paget’s disease and EMPD is/are?

a. pain
b. pruritus
c. burning sensation
d. bleeding
e. all of the above

Answer 3

Answer: B. pp.1934

Question 4

Which statement regarding Paget’s disease is INCORRECT?

a. Bilateral mammography is required in all cases, with biopsy of any detectable breast mass.
b. The transformation theory is supported by the presence of an underlying breast carcinoma in nearly all cases of MPD.
c. The use of MRI in patients with biopsy-proven Paget’s disease and negative mammogram can help identify occult breast malignancy
d. In the epidermotropic theory, malignant Paget cells arise from an underlying breast Ca and directly extend into the epidermis via the lactiferous ducts and ductules.
e. All statements are correct

Answer 4

Answer: B. pp.1936

Question 5

Which of the following should be considered as first-line study in patients diagnosed with EMPD?

a. colposcopy
b. colonoscopy
c. pelvic exam
d. Papanicolau test
e. all of the above

Answer 5

e. all of the above

Question 6

Which of the following immunohistochemical stains is POSITIVE more frequently for Secondary EMPD ONLY?

a. CK20
b. CK7
c. EMA
d. MUC1
e. MUC2

Answer 6

a. CK20

Question 7

Which is a known risk factor associated with a worse prognosis for EMPD?

a. lymphovascular invasion
b. dermal invasion > 1 cm
c. comorbidities
d. advanced age

Answer 7

a. lymphovascular invasion

Question 8

Which is generally considered the standard treatment for EMPD?

a. chemotherapy
b. surgery
c. topical corticosteroids
d. PDT with radiotherapy

Answer 8

b. surgery

Question 9

Which of the following immunohistochemical stains test POSITIVE for Paget’s disease, Primary EMPD and Secondary EMPD?

a. CK20
b. CK7
c. EMA
d. MUC1
e. MUC2

Answer 9

b.CK7

Question 10

Which drug was not proven to be a reliably curative agent in the treatment of EMPD because of the limited penetration of the drug and the inability to reach the deeper epidermal layers and adnexal structures?

a. topical imiquimod
b. vincristine
c. topical 5-FU
d. vinblastine

Answer 10

c. topical 5-FU

Question 11

Answer 11

Paget’s Disease

Question 12

Answer 12

Figure 114-1 Paget’s disease of the nipple. Erythematous and scaly plaque involving the nipple and areola.

MPD frequently presents as a unilateral, erythematous, scaly plaque involving the nipple and/or the areola (Fig. 114-1).

Question 13

Answer 13

Figure 114-2 Scrotal extramammary Paget’s disease. Moist, eroded, oozing plaque on the scrotum of an older man.

The vulva is the most commonly affected area, representing 65% of EMPD cases but less than 2% of all vulvar neoplasms. 3,9 EMPD in other sites, such as the perineum, scrotum (Fig. 114-2)

Question 14

Most common area affected in EMPD

Answer 14

Vulva

EMPD in other sites, such as the perineum, scrotum (Fig. 114-2), perianal skin (Fig. 114-3), and penis, is less common. In rare cases, ectopic EMPD has been reported in areas that are relatively free of apocrine glands, such as the chest, abdomen, thigh, eyelids, face, and external auditory canal.

Question 15

Answer 15

Figure 114-3 Perianal extramammary Paget’s disease presenting as moist, superficially eroded plaque.

Question 16

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Question 21

sensitive markers for both MPD and EMPD , as they stain Paget cells but do not typically react with epidermal or mucosal keratinocytes, helping to distinguish MPD and EMPD from pagetoid squamous cell carcinoma

Answer 21

Low-molecular-weight cytokeratin stains cytokeratin 7 (CK7) and anticytokeratin (CAM 5.2)

Question 22

Question 23

Question 24

most commonly reported symptom of paget’s disease

Answer 24

Pruritus

Question 25

how many percent of EMPD is associated with an underlying cancer?

Answer 25

20 - 30%

Question 26

This theory hypothesizes that malignant Paget cells arise from an underlying breast adenocarcinoma and directly extend into the epidermis via the lactiferous ducts and ductules (epidermotropism)

Answer 26

epidermotropic theory ## Footnote *theory favored by literature

Question 27

This theory suggests that epidermal keratinocytes on the nipple transform or degenerate into malignant Paget cells that are distinct from any underlying breast carcinoma

Answer 27

transformation theory

Question 28

What are the most common differential diagnosis of mammary paget's disease?

Answer 28

Question 29

diseases that should always be ruled out in MPD?

Answer 29

bowen disease Melanoma

Question 30

What are the most common differential diagnosis of extramammary paget's disease?

Answer 30

Question 31

diseases that should always be ruled out in EMPD?

Answer 31

Bowen disease Erythroplasia of Queyrat Melanoma

Question 32

this type of EMPD is thought to start as an in situ carcinoma that can progress by invading the dermis and subsequently metastasizing via lymphatic spread

Answer 32

Primary EMPD

Question 33

this type of EMPD arises from an underlying adnexal carcinoma or internal malignancy in approximately 20% to 30% of cases

Answer 33

Secondary EMPD

Question 34

Common visceral malignancies associated with EMPD

Answer 34

carcinomas of the colon, rectum, bladder, urethra, cervix, and prostate

Question 35

histopathologic findings of paget's disease

Answer 35

* There are groups, clusters, or single cells within the epidermis that show nuclear enlargement with atypia, prominent nucleoli, and well-defined ample cytoplasm. * Intercellular bridges are absent. * The cells may be in all levels of the epidermis, and compress, but preserve, the basal layer without junctional nest formation. * The cells may extend into the contiguous epithelium of hair follicles and sweat gland ducts. * Acanthosis, hyperkeratosis, and parakeratosis are often present. * These cells have a “pagetoid” appearance.

Question 36

Paget cells have intracellular mucopolysaccharides, with EMPD having a greater amount of mucin compared to MPD. What stains are used to stain mucin? Is this diastase sensitive or resitant?

Answer 36

Mucin - (+) periodic acid-Schiff, mucicarmine, Alcian blue, and colloidal iron Diastase RESISTANT

Question 37

Which types of paget's disease are (+) for S100?

Answer 37

NONE S100, Melan-A (also known as MART-1), and HMB-45 are useful markers to exclude melanoma and are typically negative in MPD and EMPD

Question 38

Which types of paget's disease are (+) for CK7?

Answer 38

MPD, primary and secondary EMPD

Question 39

Which types of paget's disease are (+) for CAM 5.2 and CEA?

Answer 39

MPD and primary EMPD

Question 40

Which types of paget's disease are (+) for CK20?

Answer 40

Secondary EMPD

Question 41

Which types of paget's disease are (+) for EMA?

Answer 41

MPD and primary EMPD

Question 42

Which types of paget's disease are (+) for GCDFP-15?

Answer 42

Primary EMPD Gross cystic disease fluid protein-15 (GCDFP-15) is a marker for apocrine epithelium and is more commonly positive in primary EMPD and negative in cases of secondary EMPD with an associated malignancy.

Question 43

Which types of paget's disease are (+) for MUC1?

Answer 43

MPD and primary EMPD

Question 44

marker for apocrine epithelium and is more commonly positive in primary EMPD and negative in cases of secondary EMPD with an associated malignancy

Answer 44

Gross cystic disease fluid protein-15 (GCDFP-15)

Question 45

Risk factors that appear to carry a worse prognosis

Answer 45

- lymphovascular invasion - increasing depth of tumor invasion (> 1 mm dermal invasion) - Lymph node metastasis - elevated CEA

Question 46

generally considered the standard treatment for EMPD

Answer 46

Surgery

Question 47

It was also reported that 97% of the cases treated with Mohs micrographic surgery required margins of how many cm from the clinical margin for tumor clearance

Answer 47

5 cm

Question 48