20 - 114: PAGET'S DISEASE Flashcards
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: D.
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: D. pp. 1935
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: B. pp.1934
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: B. pp.1936
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
e. all of the above
Which of the following immunohistochemical stains is POSITIVE more frequently for Secondary EMPD ONLY?
a. CK20
b. CK7
c. EMA
d. MUC1
e. MUC2
a. CK20
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
a. lymphovascular invasion
Which is generally considered the standard treatment for EMPD?
a. chemotherapy
b. surgery
c. topical corticosteroids
d. PDT with radiotherapy
b. surgery
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
b.CK7
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
c. topical 5-FU
Paget’s Disease
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).
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)
Most common area affected in EMPD
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.
Figure 114-3 Perianal extramammary Paget’s disease presenting as moist, superficially eroded plaque.
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
Low-molecular-weight cytokeratin stains cytokeratin 7 (CK7) and anticytokeratin (CAM 5.2)
most commonly reported symptom of paget’s disease
Pruritus
how many percent of EMPD is associated with an underlying cancer?
20 - 30%
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)
epidermotropic theory
*theory favored by literature
This theory suggests that epidermal keratinocytes on the nipple transform or degenerate into malignant Paget cells that are distinct from any underlying breast carcinoma
transformation theory
What are the most common differential diagnosis of mammary paget’s disease?
diseases that should always be ruled out in MPD?
bowen disease
Melanoma
What are the most common differential diagnosis of extramammary paget’s disease?
diseases that should always be ruled out in EMPD?
Bowen disease
Erythroplasia of Queyrat
Melanoma
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
Primary EMPD
this type of EMPD arises from an underlying adnexal carcinoma or internal malignancy in approximately 20% to 30% of cases
Secondary EMPD
Common visceral malignancies associated with EMPD
carcinomas of the colon, rectum, bladder, urethra, cervix, and prostate
histopathologic findings of paget’s disease
- 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.
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?
Mucin - (+) periodic acid-Schiff, mucicarmine, Alcian blue, and colloidal iron
Diastase RESISTANT
Which types of paget’s disease are (+) for S100?
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
Which types of paget’s disease are (+) for CK7?
MPD, primary and secondary EMPD
Which types of paget’s disease are (+) for CAM 5.2 and CEA?
MPD and primary EMPD
Which types of paget’s disease are (+) for CK20?
Secondary EMPD
Which types of paget’s disease are (+) for EMA?
MPD and primary EMPD
Which types of paget’s disease are (+) for GCDFP-15?
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.
Which types of paget’s disease are (+) for MUC1?
MPD and primary EMPD
marker for apocrine epithelium and is more commonly positive in primary EMPD and negative in cases of secondary EMPD with an associated malignancy
Gross cystic disease fluid protein-15 (GCDFP-15)
Risk factors that appear to carry a worse prognosis
- lymphovascular invasion
- increasing depth of tumor invasion (> 1 mm dermal invasion)
- Lymph node metastasis
- elevated CEA
generally considered the standard treatment for EMPD
Surgery
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
5 cm
