1. Martha K. Terris, M.D. Medical College of Georgia
Prostate Pathology
Martha K. Terris, M.D.
Medical College of Georgia

2. Normal
Complex glands with 2 cell layers, epithelial and basal cell layers

3. Normal
Complex glands with 2 cell layers, epithelial and basal cell layers, no nucleoli

4. Normal
HMW keratin stains basal layer

5. BPH Occurs in Transition Zone
Due to androgen stimulation & estrogen synergism

6. Histologic features: both glands and stroma can become hyperplastic
cytologically benign with 2 cell layers, bland nuclei and abundant cytoplasm
nonspecific chronic lymphocytic infiltrate is common

7. BPH
Stromal Hyperplasia
Theorized to respond better to alpha-blockade

8. Corpora amylacea may be identified (laminated eosinophilic concretions within the lumen of the gland)

9. BPH
Basal Cell Layer not always easy to identify

10. BPH
HMW keratin staining may show gaps in basal layer but will always be at least partial

11. BPH
Like normal prostate tissue, nucleoli are not typically identified

12. BPH
Branching glands, corpora amylacea, no nucleoli

13. BPH Nodule of glandular hyperplasia
Theorized to respond better to finasteride

14. BPH Nodule of glandular hyperplasia
Theorized to respond better to finasteride

15. BPH Nodule of glandular hyperplasia
Glands can be dilated with secretions

16. BPH Nodule of glandular hyperplasia
Glands can be dilated with secretions

17. Polypoid Hyperplasia
Aka Prostatic urethral polyps; Present with hematuria
Small polyps demonstrating typical prostatic-type epithelium; PSA and PAP positive; behavior is benign and recurrence after TUR is unusual.
Histology can also be adenomatoid (nephrogenic adenoma; frequent recurrence) and adenomatous (endometroid)

18. Infarcts 20-25% of BPH specimens have infarcts
Patients may present with acute retention due to a sudden increase in the size of the prostate
Gross: mottled and yellowish, or may appear hemorrhagic

19. Infarcts Histologic features: typically shows three zones
central zone of coagulative necrosis (everything looks reddish with faint outlines of the cells, like “ghost cells”)
middle zone of hemorrhage and inflammation
peripheral zone of glands with squamous metaplasia

21. Acute Prostatitis
Inflammatory infiltrate within gland lumens

22. Chronic Prostatitis
Inflammatory infiltrate surrounds the glands, involving the surrounding stroma

23. Acute and Chronic Prostatitis
Infiltrate both in lumens and surrounding glands

24. Malignant Lymphoma
Diffuse infiltration of parenchyma by small round blue cells with minimal cytoplasm
Typically the normal architecture is spared
Stains for leukocyte markers are positive

25. PIN Probable precursor lesion for prostatic carcinoma
Divided into low grade (mild dyplasia/ grade I) and high grade (moderate dysplasia/ grade 2 and severe dysplasia/ grade 3)
High grade PIN is a marker for cancer
Histologic features:
on low power, the glands appear large and complex, but more basophilic (blue) than the normal glands of BPH
basal cells are present, if only focally
high power shows prominent nucleoli, nuclear crowding and pseudostratification (piling up of the nuclei)
also: the papillary structures at low power turn out to be caused by the cellular pile-up; in BPH, the papillary structures actuallly have fibrovascular cores and therefore are true papillae.

26. PIN

27. PIN

28. Normal Gland and PIN

29. PIN

30. PIN
Papillary lumenal projections have NO fibrovascular core

31. Compare to BPH
Papillary structures each have a fibrovascular core

32. Low Grade PIN
Multiple epithelial cell layers but unlike high grade PIN, has no nucleoli

33. High Grade PIN

34. High Grade PIN
HMW keratin shows fragmented basal cell layer

35. Beware: Basal Cell Hyperplasia
Nuclei are ovoid with finely reticular chromatin and rare punctate nucleoli. The cytoplasm is pale eosinophilic or clear

36. Basal Cell Hyperplasia

37. Basal Cell Hyperplasia

38. Prostate Adenocarcinoma
Microscopic foci of cancer may begin in the 30’s, present in 70% of men by the age of 70
80% occur in the peripheral zone, 10-20% in the transition zone; most appear yellow or gray-white grossly
Histologic features:
Unlike other malignancies, neoplastic glands are very small, simple, and bland. Complexity in the prostate is generally a good sign, whereas small simple glands may herald cancer.
helpful findings: blue mucin, crystalloids, prominent nucleoli, single layer of cells (immuno)
Gleason’s grading system

39. Prostate Cancer Crystalloids
Corpora amylacea
Elongated, refract light

40. Prostate Cancer Blue Mucin

41. Prostate Immunohistology
Alpha-methylacyl-CoA-racemase (racemase) aka, P504S, is an enzyme involved in beta-oxidation of branched chain fatty acids. Moderate to strong staining is seen in prostate cancer and high-grade PIN, but not in benign prostatic tissue.
HMW cytokeratin antibody (34ß-E12) stains the cytoplasm of basal cells of the prostate. Increasing grades of PIN are associated with progressive disruption of the basal cell layer. Cancer cells consistently fail to react with this antibody.
p63 antibody stains the nucleus of basal cells. Basal cell cocktail (34 ß-E12 and p63) increases the sensitivity of the basal cell detection and reduces staining variability, thus rendering basal cell immunostaining more consistent.
PSA, PAP antibodies are useful in cases of unknown primary or very de-differentiated tumors.

42. Prostate Immunohistology
HMW keratin and p63 stain basal cell layer of atrophic benign gland
Racemase stains malignant cells

43. Gleason Grade
Gleason grading assigns prostatic malignancy a rank from 1 to 5 based on level of dedifferentiation. 1 being best. 1 and 2 are rarely used any more so really a rank from 3-5
Prostatic cancers are typically heterogenous therefore receive the sum of their two most common architectural patterns
the first number is the most prevalent pattern
the second number is the second most prevalent pattern (a minimum of 10% of the cancer volume)
Denoted the two numbers separately is the Gleason score, i.e. 4+3
the sum of the two, e.g., 7 is the Gleason sum or grade and is an excellent predictor of clinical behavior.
Sometimes a tertiary grade will be mentioned (or used as the secondary grade) if it is poorly differentiated.

44. Grade 4: “Fused” glands (no stroma separating some of the glands) or multiple lumens in a single gland.
Grade 5: No longer attempting to create glands; cells in sheets, clumps, rows, or individual.
Grades 1-3 consist of small, simple round glands with a single cell layer surrounded by stroma
Grade 1: Glands in nodular pattern
Grade 2: Glands in vaguely rounded configuration
Grade 3: Glands infiltrating between normal glands

45. Gleason Grading Do not try to assign a grade to treated tissue
Hormone therapy
Prior radiation therapy of any kind

46. Gleason Grade 1
nodules of uniform, closely-packed malignant glands, nucleoli are relatively inconspicuous

47. Gleason Grade 2
Nodular configuration but more loosely packed.

48. Gleason Grade 2
Nodular configuration but more loosely packed.

49. Gleason Grade 3
Tumor infiltrates in and among the non-neoplastic prostatic glands

50. Gleason Grade 3
Tumor infiltrates in and among the non-neoplastic prostatic glands

51. Gleason Grade 3
Tumor infiltrates in and among the non-neoplastic prostatic glands

52. Gleason Grade 4
Fused glands without completely surrounding stroma, poorly formed or multiple lumens

53. Gleason Grade 4
Fused glands without completely surrounding stroma, poorly formed or multiple lumens

54. Gleason Grade 4
Fused glands without completely surrounding stroma, poorly formed or multiple lumens

55. Gleason Grade 4
Fused glands without completely surrounding stroma, poorly formed or multiple lumens

56. Hypernephroid Gleason Grade 4
Abundant clear cytoplasm with a dot-like nucleus

57. Mucinous Gleason Grade 4
Extracellular mucin makes up at least 25% of tumor volume

58. Gleason Grade 5
Minimal gland formation, cells in sheets, clumps, cords

59. Gleason Grade 5
May need PSA stain to confirm diagnosis

60. Gleason Grade 5
Minimal gland formation, cells in sheets, clumps, cords

61. Gleason Grade 5
Minimal gland formation, cells in sheets, clumps, cords

62. Gleason Grade 5
Signet Ring Histology

63. Cribriform
Smoothly-circumscribed nodules with large ducts that are filled and distended with tumor in a cribriform pattern can be called grade 3 or 4. The presence of central necrosis in a cribriform carcinoma raises the grade to 5.

64. Gleason Grade 5
Grade 5 Cribiform with comedonecrosis

65. Seminal Vesicle
Beware of trick questions!

66. Seminal Vesicle
Look for golden-brown granules of lipofuscin pigment

67. Small Cell Carcinoma
Small round blue cells in sheets, necrosis, high mitotic rate.
“Molded” nuclei with inconspicuous nucleoli
PSA and PAP stains are typically negative and serum PSA levels may be only mildly elevated. Neuroendocrine stains positive

68. Endometroid Carcinoma
Typically arises in area of urethra/prostatic utricle
PSA and PAP positive
Often grade 3 or 4 but 5 if has necrosis

69. Transitional Cell Carcinoma
Typically involves large ducts
More cytologic atypia than prostate cancer
PSA negative

70. Squamous Cell Carcinoma
Rare in North America, more often in areas where Schistosomiasis is endemic
Histologic features include keratin pearl formation, intercellular desmosomes, etc. 

71. Rhabdomyosarcoma Average age 7 years, rapid growth
Sheets of small round blue cells with scattered strap cells (tadpole cells) having cross-striations