Stratified Cuboidal Epithelium

At a glance

Two to three layers of cuboidal cells; sturdier than simple cuboidal but still keeps a round lumen.
Common in sweat ducts, salivary duct segments, distal lactiferous ducts, and short transition zones.
Expect even nuclei, smooth basement membrane, and possible myoepithelial support depending on site.
Basal cells p63/CK5/6+, luminal cells CK7/CK19/EMA+; myoepithelial rim (skin/breast) is SMA/calponin+.

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Generalities
Eccrine / apocrine sweat duct type (skin)
Salivary gland duct type (intralobular → interlobular segments)
Mammary / lactiferous duct distal segments
Transition to stratified columnar at mucosal outlets (e.g. major salivary duct entering oral cavity, eyelid/conjunctival ducts)

Eccrine / apocrine sweat duct type (skin)

2 neat layers of cuboidal cells.
Luminal cells EMA+/CEA+, outer/basal p63+ (sometimes SMA+).
Sometimes the luminal cell has a slightly eosinophilic/apical “cuticle.”
Why mention: this is the prototype; lots of adnexal tumors mimic this.

Generalities

1. Architecture

Two (sometimes three) superposed layers of cuboidal cells (one cuboidal layer on top of another, rarely more than 3)

Why: more than one layer = better protection from lumen contents and from external compression, but keeping cells cuboidal preserves a regular, round lumen.

Luminal/superficial layer is also cuboidal (not squamous, not flattened)

Why: this keeps the lumen circular and patent — useful in ducts that open to the surface or that get squeezed.

Basal layer sits on a continuous basement membrane

Why: duct wall needs a firm base so it doesn’t collapse or detach in fibrous stroma.

Lumen is usually small and regular

Why: this is a conducting / modifying duct, not a storage cavity.

2. Cytologic Features

Cells with central, round nuclei in both layers

Why: hallmark that this is “true” stratified cuboidal, not squamous maturing upward.

Cytoplasm scant to moderate, eosinophilic to pale

Why: these cells are not doing heavy secretion like acini; they are a lining.

Minimal pleomorphism, orderly stacking

Why: normal duct lining should look monotonous; atypia here is a red flag for dysplasia or adnexal neoplasia.

Occasional apical clearing or small microvilli (esp. in sweat ducts)

Why: allows minor ion handling at the luminal surface.

3. Polarity and Attachment

Apical surface of the top cuboidal layer faces the duct lumen

Why: this is the interface that contacts sweat/saliva/milk → needs to be smooth and controlled.

Basal cuboidal cells attached to BM by hemidesmosomes

Why: ducts pass through CT, fat, sometimes muscle — they are moved and squeezed; basal cells must stay put.

Lateral surfaces of adjacent cells interlock

Why: prevents the duct wall from gaping when pressure changes.

4. Junctional Complexes

Apical tight junctions between superficial cuboidal cells

Why: keep duct contents in the lumen and prevent leakage into stroma (important for sweat and salivary ducts).

Adherens junctions (E-cadherin/catenins) along lateral borders

Why: maintain epithelial coherence in a small-diameter tube.

Desmosomes present between both basal and superficial layers

Why: ducts are subject to traction (e.g. around hair follicles, in nipple/areola); desmosomes stop tearing.

Basal attachment via hemidesmosomes / integrins to basement membrane

Why: anchors whole epithelium to the duct wall scaffold.

5. Basement Membrane / Stroma

Continuous, thin basement membrane around the duct

Why: gives a clear boundary between epithelial duct and surrounding gland/dermis.

Often surrounded by fibrous or myoepithelial tissue (organ-dependent)

Why: contraction or support from outside must not distort the epithelial tube.

6. Immunohistochemistry

(varies a bit by organ, but core pattern is similar)

Core epithelial / ductal markers:

CK7+ (most stratified ductal segments)

Why: duct-type epithelium.
CK8/18+ (simple-type keratins often persist)

Why: even stratified, it’s still gland/duct epithelium.
CK19+ (frequent in salivary / sweat ducts)

Why: small-duct/ductal phenotype.
EMA+ / CEA+ luminally

Why: ductal surface glycoproteins.

Basal/myoepithelial layer (when present around the duct):

p63+, SMA+, calponin+ (outside / basal)

Why: tells you the duct is still in its native gland unit and not an invasive carcinoma taking its place.

Negative for endothelial (CD31, vWF) and mesothelial (WT1, calretinin) markers

Why: separates from other flat/small-lumen linings.

Skin / sweat duct–specific:

Luminal cells: CEA+, EMA+
Basal cells: p63+

Why: classic eccrine duct two-layer profile.

7. Typical Anatomic Sites

Sweat gland ducts (eccrine, apocrine portions in dermis)

Why: ducts ascend through dermis, face variable pressure, and carry modified fluid → need reinforcement.
Larger ducts of salivary glands (some interlobular/striated segments can be stratified cuboidal or stratified columnar)

Why: near the oral opening, trauma and flow increase.
Ducts of mammary gland / lactiferous segments (parts)

Why: milk flow + nipple motion → stronger duct lining.
Conjunctival / eyelid-related ducts (minor)

Why: small ducts exposed to blinking/shear.

8. Function

Reinforced conduit

Why: two cuboidal layers resist collapse and abrasion better than one simple layer.

Controlled luminal environment

Why: tight junctions + viable surface cells prevent gland secretions from leaking and being altered by interstitial fluid.

Mechanical protection at duct–surface junctions

Why: where a deep gland duct meets a more exposed surface (skin, oral mucosa), the epithelium must tolerate rubbing, stretching, and pH/sweat changes.

9. Pathology / Diagnostic Use

Background for adnexal tumors: many sweat/salivary adnexal neoplasms try to recapitulate a “central duct with stratified cuboidal lining.”

Why: knowing the normal pattern helps recognize ductal differentiation (vs pure squamous).
Duct ectasia / chronic sialadenitis: epithelium may flatten or become more squamoid.

Why: pressure/inflammation can simplify the lining.
Distinguish from stratified squamous: surface cells here stay cuboidal, nuclei central, no maturation to flat anuclear squames.

Why: tells you it’s ductal, not surface mucosa.

10. Summary Logic

Why stratified? duct needs extra protection / strength.
Why cuboidal (not squamous)? duct needs to keep a round, small lumen and sometimes modify its content.
Why only 2–3 layers? more would narrow lumen too much and block flow.

Mammary / lactiferous duct distal segments

Often 2-layered cuboidal/low columnar, outer myoepithelial layer.
Hormonal/inflammatory changes can make it look “thicker.”
Why mention: background for ductal ectasia / periductal mastitis.

Salivary gland duct type (intralobular → interlobular segments)

Can be stratified cuboidal or stratified columnar depending on level.
CK7+/CK19+, luminal EMA+/CEA+, with a myoepithelial/basal rim (p63+/SMA+).
Why mention: in chronic sialadenitis or near the oral opening it can look more squamoid → easy to miscall.

Transition to stratified columnar at mucosal outlets (e.g. major salivary duct entering oral cavity, eyelid/conjunctival ducts)

Starts stratified cuboidal, becomes stratified columnar to match surface.
Why mention: so you don’t think it’s “abnormal” that it’s not cuboidal all the way.