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Mimickers of prostatic carcinoma
- 2. • Various histoanatomic structures , inflammatory & reactive condition and pathological lesions can resemble carcinoma prostate. • Present with problem if there is limited sampling in thin core needle bx. • So it is prudent to consider various other pattern before considering a diagnosis of ca prostate.
- 4. Grading of PIN PIN 1 Increased nuclear size Increased variability of nuclear size Focal crowding and multi layering PIN 2 Features of PIN 1 Hyperchromatism Occasional prominent nucleoli PIN 3 Numerous prominent nucleoli Low grade PIN PIN 1 High grade PIN PIN 2 PIN 3 Key distinguishing feature – nuclear ( nucleolar) appearance
- 5. Low grade PIN No prominent nucleoli Mild Nuclear enlargement Epithelial Proliferation and stratification Intact Basal cell layer
- 6. High grade PIN Modest stroma Overall architecture preserved Resemble benign glands Basophilic appearance Low power
- 7. Abrupt transition Epithelial proliferatn Prominent nucleoli High grade PIN High power Basal cells
- 8. High grade PIN - Types cribriform micropapillary tufted flat
- 10. Mimickers of high grade PIN Benign Central zone histology Clear cell cribriform hyperplasia Basal cell hyperplasia Malignant Cribriform acinar adenocarcinoma Ductal adenocarcinoma
- 11. Central zone vs PIN Cribriform pattern Roman bridge Papillry infoldings Pseudostratified columnar epithelium No cytological atypia
- 12. Clear cell cribriform hyperplasia Crowded Cribriform glands Prominent Basal cell layer Clear/ mild eosinophilic cytoplasm
- 13. Clear cell cribriform hyperplasia vs PIN CCCH PIN Clear cell cribriform hyperplasia lack nuclear atypia
- 14. Atypical basal cell hyperplasia vs High grade PIN Small round glands Larger glands No two distinct Cell population Atypical basal cells Undermining secretory cells Lumen not occluded Solid nests of cells Pseudostr/columnar Perpendicular to BM Round nuclei Parallel to BM Atypical basal cell hyperplasia High grade PIN
- 15. Cytology High grade PIN and infiltrating acinar ca may be indistinguishable Glands Infiltrating acinar carcinoma Small Crowded High grade PIN Larger Orderly arrangement Infiltrating acinar carcinoma vs Cribriform high grade PIN
- 16. Basal cell layer Presence excludes infiltrating carcinoma Can be absent in both Luminal acid mucin More common in infiltrating carcinoma Can be seen in high grade PIN Intraluminal crystalloids More common in acinar carcinoma Can be seen in benign glands and high grade PIN Infiltrating acinar carcinoma vs Cribriform high grade PIN
- 17. Ductal adenocarcinoma vs Cribriform high grade PIN Transition zone Rare in transition zone Larger/ back to back glands Normal sized Evenly spaced Extensive comedonecrosis No or only focal necrosis True papillary fronds Micropapillry projections Ductal adenocarcinoma Cribriform HGPIN
- 19. • Proliferation of newly formed glands that push or invade the prostatic stroma • Architectural feature – Irregular glandular contours Irregular haphazard arrangement Variation in gland size • Cytological features Nuclear enlargement Prominent peripheral macro-nucleoli(1.25-1.5 µm) Lacks a basal layer
- 20. • 2 Major category- 1. Adenocarcinoma of peripheral duct and acini • Arises from the peripheral zone. • Microscopically- anaplastic to well differentiated. • 4 major architectural patterns i) Medium sized gland pattern ii) Small gland pattern iii) Diffuse individual cell infiltration iv) Cribriform pattern
- 21. 2. Carcinoma of large duct – Microscopically following type recognized – 1. Large duct adenocarcinoma. 2. Primary transitional cell carcinoma of prostate. 3. Mixed adeno- transitional cell carcinoma.
- 23. •Gleason scoring system other than grading tool also has a role in classifying mimickers in relationship to major growth pattern.
- 25. • Broadly mimickers can be divided into 1. Those that mimic low grade adenocarcinoma ( Gleason grade<3). 2. Those that mimic high grade adenocarcinoma
- 27. TURP = Needle Atrophy Cowper’s glands Radiation atypia TURP > Needle Adenosis Basal cell hyperplasia Nephrogenic adenoma Needle > TURP Seminal vesicles Verumontanum hyperplasia Needle Colonic mucosa TURP Mesonephric hyperplasia
- 28. Adenosis • Atypical adenomatous hyperplasia . • Proliferative lesion. • Characterized by crowded small acini , usually forming small well circumscribed nodule. • Pseudoinfiltarive pattern. • Simulate small gland pattern of carcinoma.
- 29. Adenosis vs Low grade adenocarcinoma • Features that do not differentiate Back to back crowded glands Intraluminal crystalloids Medium sized [<3µ] nucleoli Scattered poorly formed glands and single cells Minimal infiltration at the periphery
- 30. Adenosis vs Low grade adenocarcinoma Lobular growth Haphazard/infiltrative Small crowded glands Admixed with larger glands May be a pure population of Small glands Adenosis Low grade aden ca Low Power
- 31. Adenosis vs Low grade adenocarcinoma High Power Huge[>3µ] nucleoli absent Occasionally huge nucleoli + Nuclear and Cytopl features same as large benign glands Differ from surrounding Benign glands Pale clear cytoplasm Amphophilic cytoplasm Occasional glands with Basal cells Basal cells absent Adenosis Low grade aden ca
- 32. Adenosis vs Low grade adenocarcinoma Adenosis Low grade adenocarcinoma High molecular weight cytokeratin
- 33. Atrophy • Affects older age group but younger age group also. • Classified as simple , simple with cyst formation , post atrophic hyperplasia, sclerotic atrophy. • Hallmark – Cytoplasmic volume loss. • Prostatic indurations • Hypo echoic lesion on transrectal ultrasound • Biopsied suspected as cancer
- 34. Atrophy Basophilic appearance Scant cytoplasm Enlarged nuclei May have prominent nucleoli Basal cell layer +
- 35. HMWCK showing a Fragmented basal layer Atrophy Scant cytoplasm Enlarged nuclei May have prominent nucleoli Basal +
- 36. Benign acinar atrophy Adenocarcinoma with atrophy Architecture • Low power • Basal cell layer • Preservation of lobular architecture •Dilated and small & distorted acini • Usually intact • Loss of lobular architecture. • Dilated and small & distorted acini. • Absent Cytology • Nuclei • Nucleoli • Normal or mild enlargement. • Usually inconspicuous • Moderate to severe enlargement. • Prominent Luminal content • Hard eosinophilic proteinaceous secretions • Basophilc mucin • Crystalloids • Rare • Rare • Rare • very common •Common • Rare
- 37. Basal cell hyperplasia • Transition zone but may also occur in peripheral zone. • A part of spectrum of nodular hyperplasia. • Characterized by 2 or more layer of basal cells with a range of growth pattern ( acinar/cribriform/solid/mixed) • Growth can be focal or form nodules. • Intermingling of the glands with basal cell hyperplasia and normal glands
- 38. Basal cell hyperplasia • Florid cases of basal cell hyperplasia may be confused with prostatic adeno carcinoma Prominent nucleoli Nuclear hyperchromatism Rare mitotic figures Nuclear enlargement Individual cell necrosis Necrotic intraluminal secretions Blue tinged mucinous secretions
- 39. Basal cell hyperplasia vs Low grade adenocarcinoma Basophilic appearance at Low magnification Basal cell hyperplasia with Prominent nucleoli
- 40. Basal cell hyperplasia vs Low grade adenocarcinoma Basophilic appearance at Low magnification Intraluminal calcifications Intracytoplasmic Eosinophilic globules
- 41. Basal cell hyperplasia vs Low grade adenocarcinoma Basal cell hyperplasia Low grade adenocarcinoma High molecular weight cytokeratin
- 42. Colonic mucosa • Features mimicking adenocarcinoma Luminal blue tinged mucinous secretions Reactive/reparative atypia • Differentiated by Goblet cells Other features of colonic tissue Potentially thickened basement membrane Lamina propria Muscularis Immunohistochemistry Prostatic markers PSA PSAP
- 43. Cowper’s glands vs Low grade adenocarcinoma Skeletal muscle Non infiltrative lobular pattern Dimorphic population of ducts and acini Abundant mucin filled cytoplasm IHC
- 44. Radiation changes Glandular atrophy Cytological atypia stromal dominance Squamous metaplasia
- 45. Radiation atypia vs Low grade adenocarcinoma Lobular Infiltrative Glands seperated by stroma Back to back glands multilayering Single cell layer Atrophic cytoplasm Abundant cytoplasm Markedly atypical nuclei Lack prominent atypia Nuclei appear degenerative Detailed nuclear features Radiation atypia Low grade adenocarcinoma HMWCK + HMWCK --
- 46. Seminal vesicle vs Low grade adenocarcinoma Numerous small glands clustered around periphery Central large dilated lumina Prominent nuclear atypia Lack mitotic figures Lipofuschin granules HMWCK will label basal cells surrounding seminal vesicle epith
- 47. Verumontanum mucosal gland hyperplasia • Proliferation of uniform , well – cumscribed , closely packed, rounded glands that contain eosinophilic secretions. • More common in radical prostatectomy specimen, but can be encountered in needle biopsy • Small and crowded verumontanum mucosal glands may simulate low grade adenocarcinoma
- 48. VMGH vs Low grade adenocarcinoma Islands of urothelium Non infitrative small glands Corpora amylacea Brownish concretions Basal cells of verumontanum glands stain + with HMWCK
- 50. Mimickers of high grade adenocarcinoma • TURP = Needle biopsy Non specific granulomatous prostatitis • Needle biopsy > TURP Xanthoma • TURP > Needle biopsy Paraganglia Clear cell cribriform hyperplasia Sclerosing adenosis • TURP Signet ring cell lymphocytes
- 51. Non specific granulomatous prostatitis • Etiology Reaction to bacterial toxins, cell debris, and secretions spilled into the stroma from blocked ducts • Mimic adenocarcinoma Per rectal examination Indurated prostate Ultra sonogram Hypo echoic lesions
- 52. PSA Elevated Histology Sheets of epitheloid histiocytes with prom nucleoli and abundant granular cytoplasm. Reactive cribriform nonneoplastic prostatic glands
- 53. Non specific granulomatous prostitis vs. High grade adenocarcinoma Sheets of epitheloid cells Some with prom nucleoli With abundant granular cyto Reactive benign cribriform prostatic gland Inflammatory cells
- 54. clear cell cribriform hyperplasia vs. High grade adenocarcinoma Clear/pale cytoplasm Prominent basal cell layer No nuclear atypia Clear cell cribriform hyperplasia Low power – nodular pattern
- 55. Sclerosing adenosis Well formed variable sized glands Single cells Cellular and myxoid Spindle cell stroma
- 56. Sclerosing adenosis vs High grade adenocarcinoma Pale cytoplasm Bland nuclei Spindle cells Thickened basement like structure Basal cell layer
- 57. Sclerosing adenosis vs High grade adenocarcinoma Muscle specific actin S-100 protein
- 58. Xanthoma vs. High grade adenocarcinoma (Hypernephroid pattern) Well circumscribed Clustering of uniform cells with benign nuclei Admixed with other inflammatory cells IHC Histiocytic markers Vacuolated cytoplasm
- 59. Prostatic paraganglia vs. Fused gland pattern( gleason 4) Small, solid nests of cells with hyper chromatic nuclei but absent nucleoli Clear or amphophilic cytoplasm Zellballen arrangement Capillaries and fibrous stroma IHC Neuroendocrine marker – chromogranin
- 60. Signet ring like changes in Nonepithelial cells ( Lymphocytes & stromal cells) Signet ring like morphology Secondary to thermal injury (in TUR specimen)
- 62. Transitional cell carcinoma on needle biopsy • Urothelial carcinoma on needle biopsy is rare. • Can mimic prostatic adenocarcinoma on Per rectal examination Ultrasonogram Elevated serum PSA There may be no concurrent history of urothelial carcinoma in the bladder
- 63. Transitonal cell carcinoma vs Poorly differentiated adenocarcinoma Nests of tumour Necrosis common Squamous differentiation may be seen Cytology High nuclear pleomorphism Variably prominent nucleoli Increased mitotic activity Stromal inflammation Sheets,individual cells or cords Necrosis rare Unusual Cytology More uniform nuclei Large, central, eosinophilic nucleoli Infrequent mitotic figures Lack inflammation Transitional cell carcinoma Poorly diff adenocarcinoma
- 64. Summary • There are a wide variety of patterns and processes that may be confused with one or more of the diverse patterns of prostatic carcinoma. • Recognition of this differential diagnosis coupled with careful routine microscopy will lead to a correct diagnosis.
- 65. • However ancillary immunohistochemical studies aimed at identifying prostatic basal cells, prostatic secretory cells , neuroendocrine cells and inflammatory cells may be required to resolve a diagnostic dilemma • The new marker a-methylacyl-CoA racemase (P504S) appears to be of value in supporting a diagnosis of adenocarcinoma,especially when one is dealing with small foci.
- 66. References • Prostate biopsy interpretation Jonathan I Epstein Ximing J. Yang • Sternberg’s diagnostic surgical pathology • Ackerman surgical patholgy • Benign mimickers of prostatic adenocarcinoma – John R Sringley ( Modern pathology) • Psudoneoplastic mimickers of prostate Ca. ( Archives Patho lab medicine 2010). • Pathology of prostate Christopher S. Foster David J. Bostwick • A visual survey of urologic pathology Dharam M Ramnani
- 67. THANK YOU