Tubular/Cribriform Carcinoma
Key Facts
Terminology
Tubular carcinoma (TC) and cribriform carcinoma (CC) are well-differentiated carcinomas
Etiology/Pathogenesis
Frequently associated with low-grade DCIS, flat epithelial atypia (FEA), and LCIS
Similar molecular alterations shared by TC, DCIS, and FEA
Suggests precursor role and possible biologic progression
Clinical Issues
60-70% present as nonpalpable mammographically detected lesions
Most patients have small carcinomas and negative lymph nodes at presentation
Pure TC and CC have excellent prognosis
Virtually always strongly ER positive
Patients may be adequately treated with adjuvant hormonal therapy alone
Favorable prognosis restricted to tumors consisting almost entirely of tubular or cribriform patterns
Top Differential Diagnoses
Sclerosing adenosis
Microglandular adenosis
Complex sclerosing lesion
Low-grade adenosquamous carcinoma
Syringomatous adenoma
Well-differentiated ductal carcinomas
Cribriform DCIS
Adenoid cystic carcinoma
 Tubular carcinoma is a special histologic type of breast cancer associated with a low metastatic potential. Favorable prognosis is restricted to tumors that consist entirely of tubular elements  . |
 Cribriform carcinoma is often seen in conjunction with tubular carcinoma, and mixed tubular and cribriform growth patterns are frequently encountered. These carcinomas have an excellent prognosis. |
TERMINOLOGY
Abbreviations
Tubular carcinoma (TC)
Cribriform carcinoma (CC)
Definitions
TC and CC are very well-differentiated carcinomas that have low metastatic potential and excellent prognosis
ETIOLOGY/PATHOGENESIS
Molecular Pathology
TC is frequently associated with
Low-grade DCIS (LGDCIS) (˜ 90% of cases)
Columnar cell change (95-100% of cases)
Lobular neoplasia (ALH and LCIS; 15-55% of cases) (“Rosen triad”)
In the majority of cases, columnar cell change is associated with flat epithelial atypia (FEA)
Molecular analysis reveals similar genetic alterations shared by FEA, LGDCIS, and TC
Frequent loss of 16q and gain of 1q
May represent biological progression along low-grade breast neoplasia pathway
Supports a possible precursor role for LGDCIS and FEA progressing to TC
Associated lobular neoplasia has not been shown to share the same genetic changes
Gene expression profiling shows that TC and CC are within the luminal A group of cancers
CLINICAL ISSUES
Epidemiology
Incidence
1-4% of breast cancers in unscreened populations
10-30% of screen-detected breast cancers
Age
Most common in women in their 50s to 60s undergoing mammographic screening
Presentation
60-70% present as nonpalpable, mammographically detected irregular masses
Most patients have small carcinomas (< 2 cm) and negative lymph nodes at presentation
More likely to be detected by mammography than other cancers
Multicentric involvement of ipsilateral breast is present in 20-50% of patients
Prognosis
TC and CC have excellent prognosis compared with other types of breast cancer
Favorable prognosis restricted to TC and CC that conform to strict histologic criteria
> 90% of the carcinoma must consist of well-formed tubules &/or cribriform areas
Few patients (10-20%) have positive nodes; may not impact overall survival
Multifocal and larger carcinomas are more likely to be associated with lymph node metastases
In general, only 1-3 nodes are involved
IMAGE FINDINGS
Mammographic Findings
Small irregular mass
Associated amorphous or pleomorphic microcalcifications in up to 50%, often due to secretory material in tubules
MACROSCOPIC FEATURES
General Features
Irregular gray-white mass with retraction of surrounding tissue
Size
Majority of TC are ≤ 1 cm, especially when mammographically detected
MICROSCOPIC PATHOLOGY
Tubular Carcinoma
Haphazard infiltrative proliferation of well-formed glands
Single layer of epithelial cells
No surrounding myoepithelial cell layer
Stromal myofibroblasts apposed to base of glands can mimic myoepithelial cells on H&E and IHC
Cells are low grade
Nuclei slightly larger than normal luminal nuclei (score 1 or 2 for grading)
Nucleoli are small and uniform
Chromatin is uniform
Apical cytoplasmic snouts are common
Mitoses are rare
Tubules have open lumens and angulated contours with tapering ends
> 90% of tumor should demonstrate characteristic tubular morphology to be considered TC
Calcifications may be associated with secretory material in lumens
Desmoplastic stromal reaction should be present and may be prominent
Prominent stromal elastosis may be present in some cases
Tubules often invade around normal ducts and lobules
Lymph-vascular invasion is highly unusual
TC frequently associated with low-grade DCIS
DCIS typically has cribriform and micropapillary patterns
TC also frequently associated with columnar cell changes, FEA, ALH, and LCIS
Cribriform Carcinoma
Haphazard infiltration of stroma by cribriform nests imparting a fenestrated appearance
Resembles cribriform DCIS
Unlike DCIS, nests of tumor cells may be found surrounding normal structures
CC lacks myoepithelial cells
CC usually associated with desmoplastic stromal reaction
Cytologic features are similar to those of TC
ANCILLARY TESTS
Immunohistochemistry
Hormone receptors
Both TC and CC typically show high levels of ER (> 95%) and PR (> 75%) expression
If result is negative, test should be repeated to confirm
HER2
TC and CC rarely (if ever) show HER2 overexpression or gene amplification
Ki-67
Usually have a low proliferative index (usually fewer than 10% positive cells)
Myoepithelial markers
IHC is often necessary to distinguish TC from other benign adenosis lesions
TC and CC lack myoepithelial cells
Benign lesions have a myoepithelial layer, which is often prominent
Microglandular adenosis lacks myoepithelial cells but will be negative for ER and PR
Muscle markers are positive in myoepithelial cells as well as in stromal myofibroblasts
Stromal cells apposed to base of tumor cells should not be mistaken for myoepithelial cells
DIFFERENTIAL DIAGNOSIS
Sclerosing Adenosis
Circumscribed or nodular appearance
Maintains lobulocentric architecture
In unusual cases, portions of lesion can have infiltrative pattern into adjacent breast tissue
Ductal structures have compressed or obliterated lumens
Ductal structures are usually back-to-back and typically have parallel or whirling patterns
Myoepithelial cells are present and often prominent
IHC can be helpful to document myoepithelial cells
Associated FEA, ADH, or DCIS are less common than in TC or CC
Microglandular Adenosis
May show nodular or diffuse architecture
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