Prostatic Adenocarcinoma
Differential Diagnosis
Benign lesions and patterns that may be confused with prostatic adenocarcinoma
- No need to diagnose atrophy, hyperplasias, or adenoses as specific entities
- Partial Atrophy
- Retention of moderately abundant pale/clear cytoplasm lateral to the nuclei may produce pale glands that lack the blue appearance of atrophy
| Partial Atrophy |
Carcinoma |
| Frequently merges with atrophic glands |
Distinct population from adjacent benign glands |
| Apical cytoplasm typically lost with preservation of lateral cytoplasm, separating the nuclei |
Apical cytoplasm typically preserved or increased while lateral is lost resulting in nuclear crowding |
| Bland nuclei, lacking enlarged nucleoli |
Large atypical nuclei with large nucleoli frequently present |
| Lacks infiltrative pattern |
Infiltrative pattern usually present |
| Basal cell markers positive, but may be decreased |
No basal cells |
Non-straightforward cases should be resolved with IPOX stains for basal cell markers
- Post-atrophic Hyperplasia
- Tightly packed very small cytologically bland glands
- Glands look blue at low power because of scant cytoplasm
- Usually near or around a larger duct
| Post-atrophic Hyperplasia |
Carcinoma |
| Usually related to a large duct |
Haphazard infiltrative pattern |
| Bland nuclei |
Large atypical nuclei with large nucleoli usually present |
| Basal cell markers strongly positive |
Basal cells absent |
| Stroma typically sclerotic |
No sclerosis of stroma |
Non-straightforward cases should be resolved with IPOX stains for cell markers
- Basal Cell Hyperplasia
- Usually fills many small glands
- Involved glands look blue from crowded nuclei with scant cytoplasm
| Basal Cell Hyperplasia |
Carcinoma |
| Smooth borders, lobular pattern |
Infiltrative pattern |
| Usually produces a pattern of small blue glands with scant cytoplasm |
Low grade carcinomas are rarely blue in appearance as most have a moderate amount of pale or amphophilic apical cytoplasm |
| Residual luminal secretory population may be focally identified as a distinct population |
Carcinoma cells are typically uniform |
| Bland nuclei |
Large atypical nuclei usually present |
| Nucleoli are easy to find but are small to moderate size |
Nucleoli may be quite large |
| Basal cell markers strongly positive |
Basal cells absent |
Non-straightforward cases should be resolved with IPOX stains for basal cell markers
- Clear Cell Cribriform Hyperplasia
- Big cribriform nodules of clear cells, generally rather obviously hyperplastic in spite of the cribriform pattern
| Clear Cell Cribriform Hyperplasia |
Carcinoma |
| Smooth borders, lobular pattern |
Infiltrative pattern |
| Uniform, bland nuclei without prominent nucleoli |
Large atypical nuclei usually present |
| Nucleoli inconspicuous or absent |
Nucleoli may be quite large |
| May be associated with cellular BPH-type stroma |
Lacks BPH type-stroma or reactive stroma |
| Basal cell markers positive |
Basal cells absent |
Non-straightforward cases should be resolved with IPOX stains for basal cell markers
- Adenosis (Atypical Adenomatous Hyperplasia)
- A benign lesion of no significance other than it simulates carcinoma
- Occurs only in the transitional zone
- Only rarely presents in a needle biopsy
- Primarily seen in TURP and prostatectomy specimens
- Well circumscribed tightly packed, largely uniform glands
- This is not a diagnosis for a small group of suspicious glands (see ASAP)
- May be sharply circumscribed over only part of the nodule
- Small uniform glands frequently merge with larger glands with the same nuclear and cytoplasmic features
- Some features suggestive of carcinoma may be seen;
- Prominent nucleoli seen in 40% of cases, but not the macronucleoli (>3 μ) seen in many carcinomas
- Crystalloids seen in about 40% of cases
- Acidic luminal mucin seen in 2% of cases
- Principal differential diagnosis is Gleason grade 2 carcinoma
- Distinction requires IPOX stain for basal cells
- Basal cells may be decreased in Adenosis
- Demonstration of any basal cells in the population indicates adenosis in this context
- Carcinoma must lack basal cells completely
- With the advent of IPOX stains, we rarely diagnose Gleason grade 2 carcinoma and never grade 1 carcinoma; most are adenosis
- Sclerosing Adenosis
- Dense spindled stroma containing compressed, distorted epithelial elements
- Entrapped epithelium ranges from small acini to cords and single cells
- Basal cells present with unique immunologic profile
- Usual markers positive (p63, HMWCK)
- Also express myoepithelial markers (smooth muscle actin, S100)
| Sclerosing Adenosis |
Carcinoma |
| Prominent sclerotic stroma |
Typically no stromal response in prostate |
| Basal cell markers strongly positive (p63, HMWCK) |
Basal cells absent |
| Myoepithelial markers positive in basal cells (smooth muscle actin, S100) |
Basal cells absent |
| Lacks cytologic atypia and macronucleoli |
May have cytologic atypia inclucing macronucleoli |
Non-straightforward cases should be resolved with IPOX stains for basal cell and myoepithelial markers
- Nephrogenic Adenoma
- Periurethral (and bladder/ureter) and may involve adjacent prostate
- Infrequent in needle biopsies but may appear in TURPs.
- Tubulocystic and papillary patterns usually combined
- Lined by a single layer of cells, frequently hobnailed
- May cause diagnostic problems if tubular pattern predominates
- Nephrogenic adenoma lacks HMW keratin/P63 positive basal cells and is racemase positive and may express prostatic acid phosphatase
| Nephrogenic Adenoma |
Carcinoma |
| Papillary and cystic patterns usually also present |
Papillae and dilated cystic areas uncommon in low grade carcinoma |
| Prominent peritubular basement membrane |
Lacks basement membrane |
| PAX8, CK7 positive |
PAX8, CK7 negative |
Non-straightforward cases should be resolved with IPOX stains
- Seminal Vesicle and Ejaculatory Duct
- Nuclear pleomorphism and complex architecture may falsely suggest malignancy
- (Prostatic adenocarcinoma involving the seminal vesicles can be seen on needle biopsy and should be reported)
| Seminal Vesicle / Ejaculatory Duct |
Carcinoma |
| Marked nuclear pleomorphism |
Marked nuclear pleomorphism is unusual in prostate carcinoma |
| Indistinct smudged chromatin |
Chromatin and nucleoli usually distinct |
| Cytoplasmic lipofuscin nearly always present |
Lipofuscin rarely seen in carcinoma |
| May have nuclear pseudoinclusions |
Nuclear pseudoinclusions rare |
| Surrounding muscular wall with a large central luminal space may identifiable in some biopsies |
Lacks a defined muscular wall and large central luminal space |
| Basal cell markers positive, prostate markers negative |
Basal cells absent, prostate markers positive |
Non-straightforward cases should be resolved with IPOX stains for prostate and basal cell markers
| Cowper Gland |
Prostatic Adenocarcinoma |
| Lobular architecture with central ducts |
Infiltrative pattern |
| Mucin filled cytoplasm, PASd+ |
Mucinous cytoplasm unusual |
| No nuclear atypia or prominent nucleoli |
Atypical nuclei, frequently large nucleoli |
| Basal cells markers positive, frequently smooth muscle actin positive |
No basal cells |
| PAP negative (PSA may be positive) |
PAP and PSA positive |
Non-straightforward cases should be resolved with IPOX stains for prostate and basal cell markers
