CASE 16

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CASE 16

• L. Priya Kunju, M.D.
• Assistant Professor
• Department of Pathology
• The University of Michigan

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Case History

• 71Y Male with previous history of urinary
  bladder cancer
• Underwent transurethral resections twice within
  last 12 months

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Diagnosis
Nephrogenic Adenoma (Nephrogenic Metaplasia)
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Nephrogenic Adenoma

• Composed of small tubules that resemble renal
  tubules
• Generally thought to be a benign metaplastic
  response of urothelium to injury/insult.
• Study (Mazal et al, 2002) on renal transplant
  patients have suggested NA is derived from shed
  renal tubular cells.

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Nephrogenic Adenoma

• Predominant in males ( 21)
• 4-81 Y
• (one-third cases lt30Y, 10 in children)
• Arise in setting of
• Past GU surgery 60
• Calculi 14
• Trauma 9
• Renal transplantation 8

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Nephrogenic Adenoma

• Sites
• Urinary Bladder 80
• Urethra 12
• Ureter 8
• Gross
• Papillary
• Polypoid (dome shaped)
• Sessile (friable, velvety)
• Size
• Majority lt1.0 cm (62)
• Rarely large 4-7 cm ( 10)
• Multifocal 18

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Nephrogenic Adenoma Microscopic Features

• Glandular lesion
• Predominantly lamina propria based with/without
  surface (mucosal) involvement
• Papillary, polypoid, tubular, cystic
  (vascular-like), or rarely solid
• Cuboidal, columnar, hobnail or signet ring cells
  with eosinophilic or clear cytoplasm
• Eosinophilic colloid-like secretions and/or blue
  mucin
• No significant cytologic atypia degenerative
  nuclear atypia may be present

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Nephrogenic Adenoma typical papillary
architecture
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Nephrogenic Adenoma tubules cysts with
hob-nail cells
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Nephrogenic adenoma

• Useful Diagnostic Features
• Distinctive architectural patterns of NA
  papillary, tubular, vascular-like dilated tubules
• Edematous stroma
• Associated inflammation
• Thickened basement membrane around tubules
• No significant cytologic atypia or mitosis
• Eosinophilic colloid-like secretions

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Predominant papillary architecture underlying
edematous stroma with associated inflammation
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NA with tubules surrounded by hyaline collars
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NA with cysts and tubules filled with colloid
like material
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Nephrogenic adenoma Features that can cause
concern

• Degenerative nuclear atypia especially within
  hobnail cells
• Haphazhard distribution of tubules containing
  blue mucin
• Tubules lined by a single cell with compressed
  nucleus simulating signet ring cells

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NA with vascular-like structures hob nail
degenerative atypia
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NA Typical tubules with blue mucin
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NA with tubules containing mucin , signet ring
cells degenerative cytologic atypia
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Nephrogenic adenomaFeatures that can cause
concern

• Degenerative nuclear atypia especially within
  hobnail cells
• Haphazhard distribution of tubules containing
  blue mucin
• Tubules lined by a single cell with compressed
  nucleus simulating signet ring cells
• Extension into muscularis mucosae and/or
  superficial muscularis propria
• Prominent fibromyxoid change in stroma with
  compressed spindle cells and distorted tubules

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NA with pseudo-infilterative pattern into muscle
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Nephrogenic AdenomaImmunohistochemistry
AMACR Positive
CK 7 Positive
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Nephrogenic adenomaImmunohistochemistry
P63 Negative
Pax 2 Positive
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Nephrogenic Adenoma Clinical Significance

• Benign
• Can recur
• Diagnostic Pitfall

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Nephrogenic adenoma Differential Diagnosis

• Surface Lesions (papillary)
• Urothelial papilloma
• PUNLMP or Low-grade papillary UC
• Involving deep lamina propria /or superficial
  muscle
• Prostatic adenocarcinoma
• Urothelial carcinoma with bland histology
• Hob-nail cells, solid growth of clear cells
• Clear cell adenocarcinoma of urinary bladder
  (rare)

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Nephrogenic Adenoma of Prostatic Urethra

• Morphology
• Tubules including signet ring-like tubules
• Cytologic atypia prominent nucleoli and/or
  blue mucin
• Imunohistochemistry
• HMWCK Variable
• Negative (40-50)
• P63 Negative
• PSA Predominantly Negative
• Focal (30)
• AMACR Positive

Morphologic Immunohistochemical Mimic of
Prostate Cancer
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Nephrogenic Adenoma of Prostatic Urethra Useful
Diagnostic Features

• Distinctive architectural patterns of NA
• Adjacent urothelium
• Associated inflammation
• Degenerative type nuclear atypia
• Hyaline sheath around tubules
• Eosinophilic colloid-like secretions
• Positive CK 7, AMACR Pax 2

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AMACR positive
PAX 2 positive
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Urothelial carcinoma (UC) with bland histology

• Benign Mimics
• Nested variant of UC Florid von Brunn nests
• Nephrogenic adenoma
• UC with small tubules Cystitis glandularis
• Nephrogenic Adenoma
• Microcystic UC Cystitis Cystica
• Cystitis glandularis
• Nephrogenic Adenoma
• Significance Diagnostic pitfall in small
  biopsies
• Aggressive clinical course (Nested variant)

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Urothelial Carcinoma Nested Variant

• Irregularly sized, small, closely packed nests
• Lumina formation within nests and/or tubules
• Variable stroma Scant, focally desmoplastic or
  loose myxoid rarely edematous
• Infiltrative base muscularis propria invasion
  common
• Low grade nuclei (bland cytology) greater
  random cytologic atypia /pleomorphism focally
  in regions of deep invasion
• IHC CK7, CK 903 and p63 positive

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Small crowded nests of nested UC
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Nested UC invading muscle
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Nested UC with cytogic atypia and tubules
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Urothelial carcinoma with small tubules

• Frequently admixed with nested variant
• Almost exclusive component of small to medium
  size tubules
• Tubules lined by attenuated urothelial cells
• Biologic Significance unclear

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Microcystic Urothelial Carcinoma

• Rare
• Widespread cystic change with nests of UC or UC
  with glandular differentiation
• Cytologically bland
• Marked variation in size and shape of epithelial
  formations and haphazard infiltrative growth
  pattern
• Biologic Significance unclear

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Clear Cell Adenocarcinoma

• Rare
• Female predilection
• Urethra more common
• Tubular, cystic, papillary and/or solid
  architecture
• Prominent nuclear atypia
• Hob-nail cells and solid growth of cells with
  clear cells
• Frequent mitosis and necrosis

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Clear cell adenocarcinoma with solid growth
prominent nuclear atypia
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Take Away

• NA is a benign metaplastic response of urothelium
  to injury
• NA has a broad histologic spectrum
• IHC CK 7, AMACR and Pax 2 Positive
• p63 negative.
• PSA, 34ßE 12 Variable
• Awareness of NA as a diagnostic pitfall in
  diagnosis of Prostate adenocarcinoma and
  Urothelial carcinoma with bland histology (esp.
  nested variant)

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Take Away

• Nested variant of UC shows aggressive clinical
  course high frequency of progression with
  metastasis and death
• Significant diagnostic pitfall in small biopsies
• Composed of tightly packed ,often confluent
  nests, with/wout tubules, predominantly bland
  cytology with random cytologic atypia,
  infiltrative base
• IHC CK7, p63 and HMWCK Positive

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THANK YOU