Definition/General

Introduction:
-Collecting duct carcinoma is a rare, aggressive subtype of renal cell carcinoma
-Represents <1% of all RCCs
-Arises from collecting ducts of Bellini
-Shows poor prognosis
-Also called Bellini duct carcinoma.
Origin:
-Originates from epithelium of collecting ducts
-Located in renal medulla
-Shows high-grade features
-Associated with complex genetic alterations
-Develops from distal nephron.
Classification:
-WHO 2022: Collecting duct carcinoma
-Single entity with aggressive behavior
-High-grade by definition
-Medullary location characteristic
-Poor differentiation.
Epidemiology:
-Peak incidence 5th-6th decades
-Male predominance (2:1)
-Very rare (<1% of RCC)
-Aggressive clinical course
-Poor survival rates.

Clinical Features

Presentation:
-Flank pain
-Gross hematuria
-Palpable mass
-Weight loss
-Advanced stage at presentation
-Metastases often present.
Symptoms:
-Abdominal/flank pain
-Hematuria
-Constitutional symptoms
-Back pain
-Fatigue
-Anemia
-Cachexia.
Risk Factors:
-No specific risk factors identified
-Possible genetic predisposition
-No association with common RCC risk factors
-Sporadic occurrence.
Screening:
-CT/MRI imaging
-Medullary location suspicious
-Irregular margins
-Heterogeneous enhancement
-Staging workup essential.

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Gross Description

Appearance:
-Medullary location
-Gray-white, firm mass
-Infiltrative margins
-Extensive necrosis
-Hemorrhage common
-Involves renal sinus.
Characteristics:
-Poorly circumscribed
-Firm consistency
-Gritty texture
-Central/medullary location
-Invasion of surrounding structures
-Necrotic areas.
Size Location:
-Medullary/central location
-Variable size (3-15 cm)
-Involves renal pelvis
-Perirenal extension
-Renal vein invasion
-Lymph node metastases.
Multifocality:
-Usually solitary
-Extensive local invasion
-Early metastases
-Retroperitoneal spread
-Distant metastases common.

Microscopic Description

Histological Features:
-High-grade adenocarcinoma
-Tubular and papillary patterns
-Desmoplastic stroma
-Marked nuclear atypia
-High mitotic rate
-Extensive necrosis.
Cellular Characteristics:
-Pleomorphic cells
-High nuclear grade
-Prominent nucleoli
-Abundant eosinophilic cytoplasm
-Atypical mitoses
-Multinucleated giant cells.
Architectural Patterns:
-Tubular architecture predominant
-Papillary areas
-Solid sheets
-Cribriform pattern
-Sarcomatoid differentiation
-Desmoplastic reaction.
Grading Criteria:
-High-grade by definition
-WHO/ISUP Grade 3-4
-Marked nuclear pleomorphism
-High mitotic activity
-Necrosis common.

Immunohistochemistry

Positive Markers:
-CK7 - positive
-CK19 - positive
-CK8/18 - positive
-EMA - positive
-PAX8 - positive
-Ulex europaeus - positive
-PNA lectin - positive.
Negative Markers:
-CD10 - negative
-RCC marker - negative
-CA9 - negative
-AMACR - negative
-CK20 - negative
-PSA - negative.
Diagnostic Utility:
-CK7 positivity supports diagnosis
-Ulex europaeus relatively specific
-Negative CD10/RCC helps exclude other RCC
-PAX8 confirms renal origin
-High molecular weight cytokeratins positive.
Molecular Subtypes:
-All cases: CK7+, high-grade features
-Distal nephron markers positive
-Proximal tubule markers negative
-Collecting duct differentiation.

Molecular/Genetic

Genetic Mutations:
-Complex genetic alterations
-TP53 mutations common
-CDKN2A deletions
-NF2 mutations
-SETD2 mutations
-High mutational burden.
Molecular Markers:
-p53 pathway disruption
-Cell cycle dysregulation
-DNA repair defects
-Chromosomal instability
-High proliferation markers.
Prognostic Significance:
-Very poor prognosis
-Median survival <2 years
-High metastatic rate
-Resistance to standard therapies
-Stage at presentation critical.
Therapeutic Targets:
-Platinum-based chemotherapy
-Immunotherapy (anti-PD-1/PD-L1)
-Targeted therapy limited
-Clinical trials recommended
-Aggressive multimodal treatment.

Differential Diagnosis

Similar Entities:
-High-grade urothelial carcinoma
-Papillary RCC Type 2
-Renal medullary carcinoma
-Metastatic adenocarcinoma
-Sarcomatoid RCC.
Distinguishing Features:
-CDC: CK7+, medullary location
-Urothelial: CK20+, uroplakin+
-Papillary RCC: Better differentiation, AMACR+
-Medullary carcinoma: Sickle cell trait, younger age
-Metastatic: Organ-specific markers.
Diagnostic Challenges:
-Medullary carcinoma vs CDC
-High-grade urothelial carcinoma
-Sarcomatoid transformation
-Limited biopsy material
-Extensive necrosis.
Rare Variants:
-CDC with sarcomatoid features
-CDC with rhabdoid features
-Mixed CDC and conventional RCC.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

Radical nephrectomy specimen with tumor in medullary location

Tumor Description

High-grade carcinoma measuring [X] cm in medullary/central location

Microscopic Features

High-grade adenocarcinoma with tubular architecture, desmoplastic stroma, and marked nuclear atypia

Nuclear Grade

WHO/ISUP Nuclear Grade 4 (high-grade by definition)

pT Stage

pT[stage] - [staging details]

Margins

Surgical margins: [status]

Immunohistochemistry

CK7: Positive, PAX8: Positive, CD10: Negative, RCC: Negative

Final Diagnosis

Collecting duct carcinoma (Bellini duct carcinoma), WHO/ISUP Grade 4, pT[stage]