Chapter 121 Mammary and Extramammary Paget’s Disease

Question 1

Extramammary Paget’s disease (EMPD) is a rare neoplasm that affects _______________

Answer 1

apocrine gland-bearing skin such as the vulva, perianal region, scrotum, and penis

Question 2

MPD is almost always associated with underlying ______________________

Answer 2

in-situ or invasive intraductal adenocarcinoma of the breast (up to 98% of cases in some studies)

*malignant cells directly extend from the underlying tumor into the epidermis via the lactiferous ducts

Question 3

Primary EMPD occurs in the ___________ and accounts for the majority of patients with the disease

Answer 3

absence of underlying malignancy

Question 4

Cases of secondary EMPD are associated with an___________________.
These cases are due to_______________________

Answer 4

underlying apocrine carcinoma or internal malignancy

epidermotropic spread of malignant cells from the underlying tumor

Question 5

MPD frequently presents as a ____________ involving the nipple and/or the areola

Answer 5

unilateral, erythematous, scaly plaque

• Ulceration and weeping with an eczematous appearance
• Pain, burning, and pruritus are frequent

Question 6

Lesions of EMPD often present as a ______________

Answer 6

well-defined, moist, erythematous, scaly, eczematous plaque

• Burning and intense pruritus
• The most frequent site is the vulva, but perineal, scrotal, perianal, and penile skin

Question 7

Up to one-half of all patients with MPD have a palpable underlying breast mass.
Of those patients with a palpable underlying tumor, half have ______________________

Palpable lymph nodes are _________ in EMPD

Answer 7

axillary adenopathy due to lymph node metastasis

less frequently present

Question 8

Pathology: There are groups, clusters, or single cells within the epidermis that show _____________, _______, and well-defined ample cytoplasm

Answer 8

nuclear enlargement with atypia
prominent nucleoli

• *The cells can be within all levels of the epidermis and can compress but preserve the basal layer without junctional nest formation.
• *The cells can extend into the contiguous epithelium of hair follicles and sweat gland ducts.

Question 9

PATHOLOGY: Paget’s cells have intracellular mucopolysaccharides, with EMPD having a___________________.
As a result, cells frequently show positive staining for______________________

Answer 9

greater amount of mucin as compared to MPD

periodic acid-Schiff and diastase resistance, mucicarmine, Alcian blue at pH 2.5, and colloidal iron

Question 10

Immunohistochemistry:

Low-molecular-weight ______ and _______ are sensitive markers for both MPD and EMPD

Answer 10

cytokeratin stains cytokeratin 7 (CK7) and anticytokeratin (CAM 5.2)

***most useful keratin markers for Paget’s disease are CAM 5.2 and CK7, as they stain more than 90% of Paget’s cells but do not react with epidermal or mucosal keratinocytes

Question 11

Immunohistochemistry:
S100, Melan-A (MART-1), and HMB-45 are useful markers to exclude ________, and are typically _______ in MPD and EMPD.

___________ has been found more frequently in cases of secondary EMPD with underlying carcinoma

___________ is a marker for apocrine epithelium and is typically positive in primary EMPD

Answer 11

melanoma
negative

CK20 positivity

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

Question 12

Immunohistochemistry:
_______ is noted in both MPD and EMPD

_________ is frequently positive in primary EMPD and less commonly noted in secondary EMPD or those cases of primary intraepithelial EMPD that becomes invasive

_____ is a regulatory gene involved in intestinal proliferation and has been suggested as a useful maker in EMPD associated with underlying colorectal tumors

Answer 12

MUC1 positivity

MUC5AC

CDX2

Question 13

Immunohistochemistry:
Recent studies investigating the role of androgen receptor and 5α-reductase suggest an elevated ________ in invasive (81%) compared with noninvasive (45%) cases of EMPD

Expression of ____________ has been shown to be signicantly higher in patients with invasive lesions of EMPD as opposed to noninvasive cases

Answer 13

5α-reductase level

human telomerase reverse transcriptase (hTERT)

Question 14

_______ is required in all cases

of MPD, with immediate biopsy of any detectable breast mass

Answer 14

Mammography

Question 15

In cases of EMPD, workup is directed toward the possibility of an underlying ________

Answer 15

gastrointestinal or genitourinary neoplasm

Question 16

Overall survival in patients with MPD is affected by __________ and ________

Answer 16

lymph node status and the presence of an underlying breast mass

Question 17

The prognosis for primary EMPD confined to the ______ is excellent with appropriate treatment

Answer 17

epidermis

**In contrast, invasive EMPD has a high rate of metastasis and carries a poor prognosis

Question 18

The depth of invasion appears to be an important prognostic factor, with microscopic invasive disease (less _____) having a more favorable prognosis as compared to those with deeper invasion

_______ has been shown to have a higher incidence of death from the disease as compared to other vulvar EMPD locations

Answer 18

than 1 mm

Clitoral EMPD

Question 19

The most common sites of metastases are ______ followed by ______

Answer 19

lymph nodes

bone and lung

Question 20

_____ remains the standard definitive treatment of MPD

Answer 20

Mastectomy

Question 21

___, ___, ___ is recommended treatment of MPD based on lymph node status and specific features of the primary tumor

Answer 21

Adjuvant therapy with radiation, chemotherapy, or hormonal therapy

Question 22

_____ remains the treatment of choice for EMPD

Intraoperative staining _____ is the preferred immunostain for intraoperative tissue evaluation

____ may prove beneficial for those patients with increased risk of lymph node involvement and metastasis (i.e., ______, _______)

Answer 22

Surgery

**In addition, more radical and extensive surgeries are associated with lower rates of local recurrence of EMPD

with CK7

SLNB
dermal invasion of Paget’s cells, elevated CEA

Question 23

Mohs:
Ninety-seven percent of the cases treated with MMS required margins of ______

The _______ recurrence rate with 2 cm margins is consistent with what is seen in various reports of EMPD treated with standard wide excision.
This further validates a potential benefit of _______________ for complete peripheral and deep margin mapping and reduces the possibility of residual tumor

Answer 23

5 cm from the clinical tumor margin

40% expected
frozen horizontal sectioning

Question 24

Radiotherapy:
may be indicated in those patients who are ______ or _______ due to extensive surgery that is often required for curative treatment

Answer 24

poor surgical candidates or are concerned with the risk of compromising genitourinary function

Question 25

_____ may be useful as a preoperative adjunctive treatment to highlight the subclinical extent of disease before MMS or for early postoperative detection of recurrence.

Answer 25

5-FU

Question 26

PDT may be considered in patients who are________, _________, _______

Answer 26

poor surgical candidates,
are at risk for significant functional morbidity due to the anatomic location of the disease, or
have recurrent postsurgical disease