Simple Cuboidal Epithelium

At a glance

Single layer of boxy cells with central nuclei; more cytoplasm than squamous, less height than columnar.
Core jobs: secretion, absorption, conduit lining (kidney tubules, small ducts, follicles).
Look for microvilli/brush border in high-transport settings and basal infoldings in ion-pumping cells.
Markers: CK8/18/19, EMA; organ-specific PAX8 in renal/thyroid, thyroglobulin/TTF-1 in thyroid.

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Generalities
Renal tubule–type simple cuboidal
Thyroid follicular epithelium (simple cuboidal → low columnar)
Small excretory/intercalated ducts of glands

Generalities

1. Architecture

Single continuous layer of cuboidal epithelial cells (one layer, cells about as tall as they are wide)

Why: one layer = short diffusion/transport path; cuboidal (not flat) = more cytoplasm = cell can actually do work (pump, secrete, resorb).

Cells with round to slightly oval, centrally placed nuclei (nucleus sits in the middle, not squashed to apical/basal)

Why: equal apical and basal cytoplasm → cell can polarize transport in either direction.

Cell outline usually polygonal in surface view (looks like squares/hexagons tiled together)

Why: this packing closes gaps so the tubule/duct lumen stays smooth.

Supported by a continuous basement membrane (thin, PAS+ sheet under the cells)

Why: small tubules/ducts would collapse without a scaffold; BM also defines where regeneration should stop.

2. Cytologic Features

Cytoplasm moderate, eosinophilic to pale (more than squamous, less than tall columnar)

Why: needs room for mitochondria, ER, Golgi, transporters — classic for secretory/absorptive epithelia.

Nuclei round, open chromatin, inconspicuous nucleoli (bland-looking)

Why: these are normal, low-grade working cells, not rapidly atypical proliferations.

Cell borders may be indistinct on H&E (adjacent cells look “fused”)

Why: lateral interdigitations and tight junctions blur borders — common in renal tubules.

Low pleomorphism in normal locations (cells look very similar to each other)

Why: uniformity = healthy secretory/absorptive lining; variation = injury, metaplasia, neoplasia.

3. Polarity and Attachment

Apical surface faces the lumen of a tubule/duct/follicle (the “inside” of the tube or the thyroid follicle)

Why: this is where the cell either puts secretions out or picks fluid/solutes up.

Apical modifications may be present (short microvilli, brush border in PCT)

Why: microvilli increase apical area → more transporters → more reabsorption/secretion.

Basal surface rests on basement membrane

Why: anchors the cell and separates it from capillaries / interstitium supplying nutrients.

Basal infoldings may be present (esp. in ion-transporting cuboidal cells, e.g. kidney, striated ducts)

Why: infoldings increase basal membrane area → more Na⁺/K⁺-ATPase → better active transport.

4. Junctional Complexes

Apical tight (occluding) junctions / zonula occludens

Why: seal the top so whatever you just absorbed doesn’t leak back between cells; also allows lumen to have a different composition than interstitium.

Proteins: claudins, occludin, JAMs

Why: these are the standard seal proteins for epithelial tubes.

Subapical adherens junction / zonula adherens (E-cadherin + catenins)

Why: links neighboring cells to the actin cytoskeleton → lets the tubule/duct keep its shape during flow.

Desmosomes (maculae adherentes) on lateral surfaces

Why: spot-strength so the epithelial tube doesn’t tear where flow or pressure changes.

Basal attachment via hemidesmosomes / integrins to BM

Why: prevents the entire epithelium from lifting or detaching — important in small ducts under pressure.

5. Basement Membrane

Continuous, well-defined BM (type IV collagen, laminin, nidogen, heparan sulfate PG)

Why: supports the epithelium, keeps separate from stroma, and acts as a selective filter.

Often closely apposed to a peritubular/periductal capillary network

Why: absorbed solutes must immediately enter blood; secreted products need building blocks from blood.

Essential for orderly regeneration

Why: if BM is intact after injury, cuboidal cells can spread along it and re-tube the structure.

6. Cytoskeleton

Actin microfilaments concentrated apically (esp. with microvilli)

Why: support the brush border and anchor tight junctions.

Intermediate filaments: simple epithelial keratins (CK8, CK18, CK19)

Why: this is the keratin profile of simple epithelia — confirms epithelial nature on IHC.

Microtubules throughout cytoplasm

Why: needed for vesicle traffic in secretory/absorptive cells (e.g. thyroid, ducts).

7. Immunohistochemistry (generic simple cuboidal)

Positive: pan-cytokeratin (AE1/AE3), CK8/18, CK19, EMA

Why: confirms “this is epithelial,” and specifically “this is simple-type epithelium,” not squamous, not endothelium.

Negative: CD31, vWF, ERG (endothelial markers)

Why: separates a flat-looking duct/tubule from vascular endothelium on small biopsies.

Organ-specific additions:

Thyroid follicular epithelium: thyroglobulin+, TTF-1+, PAX8+

Why: proves thyroid origin.
Renal tubular epithelium: PAX8+, sometimes CD10+, CK8/18+, variable EMA

Why: helps identify renal primary in metastasis or in kidney tumors with tubules.

8. Vascularity and Nutrition

Epithelium itself is avascular

Why: epithelial rule.

Nutrients/oxygen diffuse from underlying capillaries, often very close to BM

Why: cuboidal epithelium is still thin enough for diffusion; high-metabolic cells (kidney) keep capillaries right there.

High metabolic variants (PCT) have rich peritubular capillary plexus

Why: need to reclaim a lot of filtrate fast.

9. Functional Correlation

Secretion (e.g. small ducts, thyroid)

Why: cell thickness allows ER/Golgi to make and export proteins/glycoproteins.

Absorption / resorption (e.g. renal tubules)

Why: apical microvilli + tight junctions + basal pumps = vector transport.

Conduit / modification (e.g. salivary/pancreatic intralobular ducts)

Why: simple cuboidal can form a neat tube and slightly change its content (ion exchange).

Barrier (moderate)

Why: tight junctions stop back-diffusion but epithelium remains thin enough to transport.

10. Regeneration and Injury

Mitotically active at a low-to-moderate rate

Why: tubules/ducts do turn over but not as fast as stratified squamous.

If BM is preserved → rapid re-epithelialization and re-tubulation

Why: cells can migrate along BM and re-form a simple layer.

If BM is destroyed (ischemia, severe nephrotoxic injury) → may heal with flattening or fibrosis

Why: without a scaffold, cells may spread as a low, squamoid epithelium or the duct/tubule may scar.

11. Typical Anatomic Correlates

Renal tubules (proximal, distal, collecting → low cuboidal)

Why: heavy transport and fine-tuning both need a simple but “roomy” cell.
Thyroid follicles

Why: single cuboidal layer is ideal to face colloid and capillaries at once.
Small intralobular / intercalated / striated ducts in exocrine glands

Why: need a stable, uniform tube with modest modifying ability.
Ovarian surface / germinal epithelium (often low cuboidal)

Why: simple protective cover on ovary.
Choroid plexus / some ependymal modifications (cuboidal–columnar)

Why: secretion of CSF requires more cytoplasm than squamous can give.

Renal tubule–type simple cuboidal

Architecture

Single layer of cuboidal cells lining tubule lumen (one layer, cells as tall as wide)

Why: keeps lumen open while allowing active transport.
Cells with central round nuclei

Why: space on all sides for pumps/organelles.
Supported by continuous BM over peritubular capillaries

Why: reabsorbed solutes must go straight to blood.

Cytologic features

PCT: tall, eosinophilic, granular, dense brush border

Why: bulk reabsorption.
DCT: low cuboidal, paler, no brush border

Why: fine-tuning.

Polarity / surfaces

Apical: brush border (PCT) or short microvilli (DCT)

Why: regulate amount of reabsorption.
Basal: infoldings with mitochondria

Why: drive Na⁺/K⁺-ATPase.

Junctions

Apical tight junctions

Why: stop back-leak of filtrate.
Lateral interdigitations + desmosomes

Why: keep tubule wall continuous.

Immunohistochemistry (renal)

PAX8+ / PAX2+ (renal tubular lineage)

Why: defines nephrogenic origin.
CD10+ (luminal) and RCC marker+ esp. proximal-type

Why: proximal tubular phenotype; useful in tumors.
CK8/18+, CK19+ (variable)

Why: simple epithelial cytokeratins.
EMA+

Why: tubular epithelium often expresses EMA.
Vimentin+ (frequent in renal tubules)

Why: renal epithelium coexpresses mesenchymal IF.
AQP1+ (PCT, descending thin limb)

Why: identifies water-transporting proximal segments.
Megalin / cubilin+ (apical, PCT)

Why: receptor-mediated endocytosis segment.
Negative: CD31, vWF (rules out endothelium)

Function

Bulk reabsorption (PCT), fine salt/water control (DCT), acid-base (intercalated cells)

Why: simple cuboidal with polarity is ideal for vector transport.

Small excretory/intercalated ducts of glands

Architecture

Single layer of small, regular cuboidal cells around a narrow lumen

Why: stable conduit with controlled modification.
Resting on clear BM within gland stroma

Why: ducts must stay patent.

Cytologic features

Central round nucleus, scant-to-moderate cytoplasm

Why: limited but real transport/secretion.
Apical short microvilli

Why: small ion/water adjustments.

Junctions

Apical tight junction belt

Why: keep gland secretion in the lumen.
Lateral desmosomes

Why: ducts can be compressed by stroma.

Immunohistochemistry (by organ)

A. Salivary intercalated / small intralobular ducts

CK7+, CK19+

Why: ductal profile.
EMA+, CEA+ (luminal)

Why: secretory/ductal surface.
Surrounded by p63+/SMA+/calponin+ myoepithelial/basal cells

Why: confirms you are in a true ductal unit.
S100− in pure duct cells

Why: separates from acinar/oncocytic or neural components.

B. Pancreatic small ducts

CK7+, CK19+

Why: pancreatic ductal.
SOX9+

Why: ductal/progenitor identity.
MUC1+ / CFTR+ (apical)

Why: fluid/ion-secreting duct.
PAX8−, thyroglobulin−

Why: excludes thyroid/renal cuboidal.

C. Eccrine/sweat duct

EMA+, CEA+ (luminal layer)

Why: ductal secretory surface.
CK7+ (ductal parts)

Why: adnexal duct.
Basal p63+ / SMA+ cells

Why: outer ductal/basal layer present.
S100−

Why: helps vs sweat gland tumors with clear-cell or myoepithelial components.

Function

Conduct primary secretion to larger ducts/surface

Why: simple cuboidal makes a clean lumen.
Modify secretion (reabsorb Na⁺/Cl⁻, secrete K⁺/HCO₃⁻)

Why: final saliva/sweat/pancreatic juice must have the right composition.

Thyroid follicular epithelium (simple cuboidal → low columnar)

Architecture

Single layer of cuboidal cells around colloid

Why: same cell must secrete into and absorb from follicle.
Height varies with activity (flat in rest, taller with TSH)

Why: more activity → more machinery.

Cytologic features

Central/basal nucleus, moderate cytoplasm

Why: balanced secretion/absorption.
Apical microvilli and endocytic vesicles

Why: colloid resorption.

Junctions

Apical tight junctions

Why: keep colloid intraluminal.
Lateral desmosomes

Why: maintain follicle integrity.

Immunohistochemistry (thyroid)

Thyroglobulin (Tg)+

Why: specific secretory product of follicular cells.
TTF-1+

Why: thyroid (and lung) transcription factor → confirms thyroid origin.
PAX8+

Why: thyroid/renal/Müllerian, supports thyroid with Tg/TTF-1.
TPO+ (variable, better in benign/differentiated)

Why: hormonogenesis marker.
CK7+, CK8/18+

Why: simple epithelium.
Negative: salivary duct myoepithelial markers (SMA, p63, calponin)

Why: separates from salivary-type cuboidal ducts.

Function

Synthesize, store, and reclaim iodinated thyroglobulin → T₃/T₄

Why: cuboidal shape allows both secretion and resorption in one cell.