Unusual Breast Carcinomas Flashcards
Medullary carcinoma (aka invasive carcinoma of no special type with medullary pattern)
The strict criteria for this diagnosis are as follows:
1. >75% syncytial growth pattern
2. Consolidated architecture with circumscription
3. Marked-to-moderate lymphoplasmacytic infiltrate
4. Poorly differentiated tumor cells
The tumor has a high mitotic rate with frequent necrosis.
The prognosis is quite good, despite how the tumor looks, if the diagnostic criteria are applied appropriately.
Associated with women who carry BRCA1 mutations. Tumors show loss of PTEN and TP53 mutations.
Atypical medullary carcinoma lacks one or two features of medullary carcinoma. Atypical medullary carcinoma and invasive ductal carcinoma, not otherwise specified have a similar prognosis. Thus, it is important to apply the criteria STRICTLY.
Invasive carcinoma of no special type with choriocarcinomatous features
Markedly pleomorphic tumor cells that appear as two different populations, with scattered atypical mitoses throughout:
* Large, pleomorphic, multinucleated tumor cells with smudged nuclei, eosinophilic cytoplasm, occasional vacuoles, and irregular cytoplasmic projections
* Smaller, monocytoid cells
This is an extremely rare morphologic pattern for invasive carcinoima of NST. It may be associated with elevated b-hCG, but nearly 60% of patients with IC-NST also have this – so it is NOT specific for choriocarcinomatous features.
All cases reported have been in middle-aged to elderly women.
IHC: Positive for hPL and b-hCG, negative for ER/PR.
Invasive carcinoma of no special type with osteoclast-like giant cells
Giant cells are similar to histiocytes and osteoclasts and are benign.
The lesion is associated with hypervascular stroma and surrounding hemosiderin/hemorrhage. May be associated with any histologic type of carcinoma.
This is caused by tumor overexpression of RANK-L.
Invasive carcinoma of no special type with neuroendocrine differentiation
Tend to be more small cell-like with high mitotic rate than well-differentiated neuroendocrine, but you can see both.
If you have a low-grade neuroendocrine lesion, stop for a moment to consider specific breast carcinomas that can characteristically express neuroendocrine markers, like solid papillary carcinoma.
Invasive carcinoma of no special type with neuroendocrine differentiation (small cell type)
Microinvasive carcinoma
Term reserved for invasive carcinoma less than 1mm in size, often adjacent to high grade DCIS.
As you may expect, carries a better prognosis, though invasion is often multifocal. If multifocal, you can still call it microinvasive as long as no individual site is greater than 1mm in size.
This is really a resection diagnosis, not a biopsy diagnosis, as excision may reveal a greater extent of invasive carcinoma.
Invasive cribriform carcinoma
Not to be confused with adenoid cystic carcinoma! Both can occur in the breast!
Haphazard fenestrated proloferation of infiltrative cribriform nests composing >90% of the tumor. Tumor cells have low-grade, polarized nuclei with uniform chromatin distribution, small single conspicuous nucleoli, and eosinophilic cytoplasm. A desmoplastic stromal response is present, and there are no myoepithelial cells.
Rare and uncommon low-grade carcinoma with a good prognosis.
IHC: Positive for ER/PR, negative for HER2. Negative for myoepithelial markers.
Invasive mucinous carcinoma
Scattered ggroups and nests of invasive carcinoma floating in pools of extracellular mucin. Deliocate fibrous septae separate the pools. Tumor cells have low-to-intermediate grade nuclei which are round-to-oval, have regular chromatin distribution, and variable eosinophilic cytoplasm. The lesion is well circumscribed.
This is an uncommon variant which occurs in elderly women and presents as a soft, palpable mass mimicing a benign process. Has three morphologic variants:
* Pure mucinous carcinoma - type A (paucicellular) or type B (more cellular, less mucinous, often with neuroendocrine features)
* Mixed mucinous carcinoma - has both a mucinous component and a mucin-free invasive component (making up >10% of the tumor)
* Micropapillary mucinous carcinoma - where mucinous cells are arranged on micropapillae and appear to point to the walls of the pool. Worse prognosis.
IHC: Positive for WT1, EMA varoab;e meirpemdpcrome expression. Most are ER/PR positive, HER2 negative.
Molecular: Associated with GATA3 or KMT2C mutations, MAP3K1 mutations, PIK3CA mutations, and OAZ1-CSNK1G2 fusions.
DDx includes mucinous cystadenocarcinoma.
Mucinous cystadenocarcinoma of the breast
Very rare breast entity, characterized by cystic structures lined by tall columnar cells with intracytoplasmic and intracystic mucin, similar to pancreatic IPMNs or ovarian mucinous carcinomas.
Invasive micropapillary carcinoma
Very rare neoplasm that often occurs in younger patients, affects both sexes equally (which is unusual for a breast carcinoma). Nearly 67% have lymph node metastasis at presentation.
Despite having tubules, graded as Nottingham 3. Survival is not significantly worse than stage-matched invasive carcinomas of no special type.
Histologically, cuboidal-to-columnar cells with intermediate-to-high grade nuclei and granular eosinophilic cytoplasm arranged in small, hollow, morula-like clusters with an inside-out growth pattern. Surrounded by spaces with intercellular fluid and a delicate stromal network. There should be no fibrovascular cores (micropapillary), and tumor cells have reverse polarity.
IHC: Positive for MUC1, E-cadherin (basolateral), and p120 (basolateral).
Prognostic markers: ER/PR positive, 50% HER2 positive.
Metaplastic carcinoma
(category)
Invasive carcinoma with a wide spectrum of differentiation of the epithelial component towards both squamous and mesenchymal-like elements.
Subtypes are numerous, and often with some overlap or a mixture of patterns:
* Low-grade adenosquamous carcinoma
* Fibromatosis-like metaplastic carcinoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Metaplastic carcinoma with heterologous mesenchymal differentiation
Rare type of bresat cancer composing less than 1% of all breast cancers. Usually presents as a large, palpable mass.
Prognostic markers: ER/PR/HER2 negative (triple negative)
IHC: Positive for TRPS1, p63, CK5/6, AE1/AE3, SOX10 (50%), negative for CK7, negative for CD34.
SMA, CD10, desmin, and beta catenin are variable.
Molecular: Mutations in TP53 (65%), PIK3CA (60%), TERT promoter (45%), PTEN (15%), NF1 (15%), PIK3R1 (10%), AKT (5%), Wnt, and RB1.
Low-grade adenosquamous carcinoma (metaplastic carcinoma variant)
Well-developed, rounded glands and tubules with assocaited solid squamous nests infiltrating through desmoplastic stroma. Sometimes associated with a “cannon ball” lymphoid aggregate.
Good prognosis.
Fibromatosis-like metaplastic carcinoma
Bland spindled cells with pale eosinophilic cytoplasm and slender nuclei, with mild atypia (or may be plump and epithelioid) in the stroma and variable collagen. Often arranged in fascicles.
Good prognosis.
Spindle cell carcinoma (metaplastic carcinoma)
Atypical spindle cells with a variety of architectural patterns (fascicular, herringbone). Spindle cells are elongated to plump with moderate-to-high-grade cytologic atypia. There is often associated inflammation. This category includes a spectrum of tumors from sarcomatoid SCC to myoepithelial carcinoma.
Worse prognosis.
Squamous cell carcinoma of the breast (metaplastic carcinoma)
Pure SCC is often cystic. The most imporant thing in this setting is to exclude a metastasis.
Worse prognosis.
Metaplastic carcinoma with heterologous mesenchymal differentiation
Essentially chondrosarcoma and the heterologous elements may include chondroid, osseous, or rhabdoid components.
Epithelial and mesenchymal components can have variable atypia; extensive sampling is often necessary to find the epithelial component and exclude a primary sarcoma of the breast.
