Papillary Breast Lesions Flashcards
Intraductal papilloma
Papillary projections with fibrovascular cores, covered by epithelial and myoepithelial cell layers. May have superimposed proliferative changes (UDH, apocrine metaplasia, sclerosing adenosis, duct ectasia) or be colonized by a malignancy.
Can be sclerotic or undergo infarction, especially after biopsy.
Broken into two categories:
Small duct papilloma - located peripherally within a TDLU and usually there are multiple. Relative risk of carcinoma is 3-fold. Usually less than 1 cm in size, not readily palpable.
Large duct papilloma - Centrally located within lactiferous ducts, usually solitary. Risk of carcinoma is 2-fold.
Molecular: PIK3CA (40%), AKT1 (30%) activating point mutations. About 50% of all papillomas have at least one of these mutations.
Staining of myoepithelial cells: Present around rim and in papillae.
Papilloma involved by DCIS
Foci of DCIS (or ADH) superimosed in an intraductal papilloma. A focal population of monotonous cells with cytologic and architectural atypia showing low-grade neoplastic ductal process. Monotonous cells will demonstrate polarization around lumina.
Focus less than 2 mm, ADH
Focus greater than or equal to 2mm, DCIS
Staining of myoepithelial cells: present around rim and in papillae
Papillary DCIS
Monotonous clonal ductal epithelial cells lining arborizing filliform fibrovasculare cores that are devoid of myoepithelial cells. Nuclei can be variable based on grade and are round to oval, have regular or irregular nuclear contour, and conspicuous or inconspicuous nucleoli.
May be deceptively bland with stratified spindle cells, compact columnar cells, or clear cells.
The comedo pattern is the only clinically relevant pattern in these lesions. The neoplasm is graded based on the nuclear cytologic features:
Low grade - small, bland, monotonous cells
Intermediate grade - intermediate features
High grade: Ugly, pleomorphic cells
Staining of myoepithelial cells: Present around rim, not present in papillae.
Encapsulated papillary carcinoma of the breast
(Formerly called intraductal/intracystic papillary carcinoma)
Carcinoma composed of fine fibrovascular (papillary) fronds covered by neoplastic epithelial cells of low-to-intermediate nuclear grade. Carcinoma is most often in a cystic space with surrounding fibrous capsule.
WHO recommends classification as a Tis lesion, but it does lack myopithelial cells. This is true UNLESS there is invasion past the capsule, in which case it would be T staged as invasive.
If it DOES extend beyond the capsule, you would likely diagnose as invasive carcinoma of no special type rather than encapsulated papillary carcinoma.
VERY low risk of metastasis and very favorable prognosis (>95% survival at 10 years). Ductal cells are CK7/CK18 positive, negative for CK5/6.
Staining of myoepithelial cells: No myoepithelial cells around the rim or in the papillae
Molecular: PIK3CA hotspot mutations are present in 20% of cases.
Solid papillary carcinoma
Heterogeneous or monotonous round to spindled-shaped epithelial cells with mild to moderate nuclear atypia, and eosinophilic, granular cytoplasm lining delicate papillae. Arranged in multiple clustered and circumbscribed solid nests. Myoeptheilail cells may be sparse, but are present. Mitoses are seen and there is variable mucin within cytoplasm or lumens. May have neuroendocrine differentiation in up to 45% of cases.
Uncommon, composes less than 1% of all breast carcinomas. Typically, it is seen in older females with a palpable multinudlar mass. Associated with a good prognosis.
If entirely well circumscribed nodules are present and no invasion is present, may be called solid papilary carcinoma in-situ and classified as Tis.
If infiltrating strands or ragged borders are present, call it invasive solid papillary carcinoma.
IHC: Myoepithelial cells positive for p63, p40, calponin, and SMH. Ductal cells positive for CK7/18, negative for CK5/6, variable neuroendocrine expression (chromo/synapto/INSM1).
Prognostic markers: Almost all ER/PR positive, Her-2 negative.
Molecular: PIK3CA mutations in 25-35% of cases. Frequently gains 1p and 16q, losses in 16q.
Invasive papillary carcinoma
Monotonous neoplastic epithelial cells with low-to-intermediate grade nuclei that are round-to-oval with variable chromsatin distribution, occasionally conspicuous nucleoli arranged on fibrovascualr cores with delicate vessels.
Usually poorly-circumscribed, with an infiltrative growth pattern. Myoepithelial cells are absent. Stromal desmoplastic response where infiltration occurs at periphery.
Extremely rare breast carcinoma (less than 1% of all breast cancers). Most common in post-menopausal women but can be seen in men. Differential diagnosis includes metastasis (lung, ovary, thyroid) and other papillary breast tumors.
Majority are ER/PR positive, HER2 negative.
Nipple adenoma
Benign, epithelial proliferation composed of any or a mixture of:
* Simple ducts
* Papillomatosis / sclerosing papillomatosis
* Adenosis
* UDH
* Florid hyperplasia
Epidermis may have Toker cell hyperplasia or hyperkeratosis. Myoepithelial cells surround all ducts. May have epidermal erosion and/or hemorrhage, or focal necrosis. Often a well-circumscribed lesion, but stromal fibrosis may entrap ducts in a pattern that can resemble invasive carcinoma.
Uncommon breast lesion, most often seen in middle-aged females. Presents with an irregular or lobulated palpable breast mass that may be tender or have associated nipple discharge.
Clinically, can mimic Paget disease due to erythema, hyperkeratosis and crusting, and erosion or ulceration.
This is a BENIGN lesion, but it may recur if incompletely excised.
Molecular: PIK3CA present in 50% of cases.
The main reason to know about this is to not confuse it with invasive carcinoma.
The typical ddx for papillary breast lesions
- Papilloma
- Papilloma involved by ADH/DCIS
- Papillary DCIS
- Encapsulated papillary carcinoma
- Solid papillary carcinoma
- Invasive papillary carcinoma
How do you tell apart papillary DCIS vs DCIS involving a papilloma?
Papillary DCIS: Diffuse (no uninvolved papillae) and no myoepithelial cells within the papillae.
DCIS involving a papilloma: Focal and intra-papillary myoepithelial cells are preserved.
What is the size cutoff from ADH to low-grade DCIS within a papilloma?
3mm
NOT 2mm – it is different than the usual cutoff.
What is the #1 thing you have to exclude to diagnose invasive papillary carcinoma?
Metastasis
Particularly from thyroid and ovary
Myoepithelial cells in solid papillary carcinoma
May or may not be present in the papillae or periphery, they are irrelevant to the diagnosis.
Myoepithelial cells in encapsulated papillary carcinoma
Negative in the papillae, and most often also negative in the capsule, but not always.
