Overview: GU Pathology Flashcards by Federico Girardi

Bladder

Noninvasive Papillary Neoplasms

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Bladder

Benign
Simple papillary architecture (fibrovascular cores)
Lined by cytologically normal urothelium (no atypia)

Histology

Papilloma

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Bladder

Most common urinary tract tumor; 90% of all primary bladder tumors

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Bladder

Industrial exposure to aniline dye
Cigarette smoking
Long-term treatment with cyclophosphamide
Schistosomiasis
Analgesic abuse
Sex: M > F
Age: >50 years

Risk Factors

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Bladder

More common: ~80%
Progresses to LGUC
Genetically stable
Recurrence rate: high
Low risk of progression: <1-5% (nonaggressive)
Genetic abnormalities:
* CDKN2A deletion (encodes p16 protein)
* FGFR3 alterations (activating point mutations; ~80%)

UC Pathogenesis

Hyperplasia pathway

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Bladder

Most common urothelial tumor

LGUC

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Bladder

Less common: ~20%
Leads to HGUC
Genetically unstable
Recurrence: high
High risk of progression
Genetic abnormalities
* RAS mutation
* p53 mutation (60%)

UC Pathogenesis

Dysplasia pathway

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Bladder

Papillary architecture
Normal / increased epithelial thickness (layers)
Mild cytologic atypia & infrequent mitotic figures

Histology

LGUC

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Bladder

Papillary architecture
Marked cytologic atypia & frequent mitotic figures
Necrosis common

Histology

HGUC

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Bladder

Flat high-grade lesion (no mass)
Poorly cohesive cells often shed into urine & appear velvety on cytoscopy
20-80% progress to invasion

Histology

Flat urothelial CIS

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Bladder

Diffuse thin, finger-like, hyperchromatic cords forming tentacular pattern

Histology

Invasive UC

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Bladder

Low-grade UC

Treatment

Tumor resection
Follow-up: biopsy / urine cytology

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Bladder

High-grade non-invasive / superficially invasive UC

Treatment

Tumor resection
Biotherap: BCG, interferon
Chemotherapy

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Bladder

High-grade with deep (muscle) invasion

Treatment

Cystectomy

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Bladder

Most frequent in Middle East & along Nile Valley
Associated with chronic inflammatory processes:
* Chronic bacterial infection
* Schistosomiasis
Can be associated with renal calculi

Bladder SCC

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Bladder

Squamous differentiation:
* Intraceullar keratin
* Keratin pearls
* Intercellular bridges

Histology

Bladder SCC

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Bladder

Associated with intestinal metaplasia & bladder exstrophy
Combination of glands, mucinous pools & signet-ring cells

Histology

Bladder adenocarcinoma

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Prostate

Site of origin for most BPH

Transitional zone

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Prostate

Major site of prostatic cancer

Peripheral zone

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Prostate

Proliferation of stromal & glandular elements leading to prostatic enlargement
Very common (50% of males at age 50; 80% at age 80)
Involves central gland –> urinary obstruction

BPH

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Prostate

Irregular, nodular
Gland may be distorted
Weight may be >100 g (normal = 20-30g)

Gross Appearance

BPH

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Prostate

Nodules may be pure glands, pure stroma, or mixture
Compresses adjacent tissue

Histology

BPH

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Prostate

BPH

Treatment

Symptomatic Tx:
- Decrease fluid intake before bed
- Avoid alcohol & caffeine
Medical Tx:
- Decrease muscle tone: a-Blockers
- Shrink prostate: 5-a-Reductase inhibitors
Surgical Tx: transurethral resection of prostate (TURP)
- First-line Tx w/ recurrent urinary retention

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Prostate

Most common form of cancer in men (27%)
Only causes ~10% of cancer deaths in US
Most pts >60 yrs of age (incidence increases w/ age)
More common in African-Americans
More common in Western hemisphere

Epidemiology

Prostatic adenocarcinoma

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# Prostate 1. Age 2. Androgens 3. Environmental factors: * Increase risk: high fat intake * Decrease risk: lycopenes, Vit A, Vit E, soy 4. Genetic factors: * 1 first-degree relative = 2x risk * 2 first-degree relatives = 5x risk * Acquired somatic mutations: * 40-60% have TMPRSS2-ETS fusion genes * LOF mutations involving PTEN (TSG) | Risk Factors

Prostatic adenocarcinoma

# Prostate * Urinary obstruction * Firm, irregular nodules / masses on digital rectal exam * Elevated PSA (>10 or greater) | Clinical Presentation

Prostatic adenocardinoma

# Prostate BPH vs. Prostate Cancer | Gross Appearance

Cancer: peripheraly located; ill-defined border; yellow discoloration BPH: transitional zone / periurethral; nodular; whitish

# Prostate * Abnormal architectural pattern * Single luminal cell layer (loss of basal cells) * Enlarged nuclei * Nuclear hypochromasia * Prominent nucleoili * Mitoses / apoptosis * Amphophilic cytoplasm * Blue mucinous secretions * Pink amorphous secretions * Crystalloids | Histology

Prostatic adenocarcinoma

# Prostate Often metastasizes to lumbar spine

Prostatic adenocarcinoma | Osteoblastic metastases

# Prostate Spread to lymph nodes (usually obturators) is eventually fatal

Prostatic adenocarcinoma

# Prostate PIN-4 immunostain | Histology

Basal cells are absent in invasive prostate cancer | If basal cells are present, prostatic cancer = in situ

# Prostate Basal cell markers | PIN-4 immunostain

1. p63 = nuclear 2. CK903 = cytoplasmic | If positive, non-invasive tumor

# Prostate Racemase (P504S, AMACR) | PIN-4 immunostain

Cytoplasmic marker overexpressed in prostate cancer (both in situ & invasive) but is absent in benign cells | If positive, prostate cancer (PIN or invasive); if negative, benign

# Prostate * Basal cell markers = + * Racemase = - | PIN-4 immunostain results

Benign cells

# Prostate * Basal cell markers = + * Racemase = + | PIN-4 immunostain results

Prostate cancer: PIN (in situ)

# Prostate * Basal cell markers = - * Racemase = + | PIN-4 immunostain results

Prostate cancer: invasive

# Prostate * Lobular arrangement * Tightly packed glands | Gleason's Score

Gleason's Score: 1 | Lowest grade prostatic adenocarcinoma; very rare

# Prostate * Loose lobular arrangement * Larger glands | Gleason's Score

Gleason's Score: 2 | Very rare

# Prostate * Small infiltrative individual glands * Well-formed glands | Gleason's Score

Gleason's Score: 3 | Most common prostatic adenocarcinoma

# Prostate * Fused or poorly formed glands * Cribriform pattern | Gleason's Score

Gleason's Score: 4

# Prostate * Solid sheets with central necrosis * Individual cells | Gleason's Score

Gleason's Score: 5 | Highest grade prostatic adenocardinoma

# Grading Prostatic Adenocarcinomas Total Gleason Score

X + Y = Total Gleason Score * X = Dominant Score Pattern * Y = 2nd Score Pattern | If there is no 2nd pattern, X + X = Total Score

# Prostate * Prostatic duct retains myoepithelial layer * Ductal epithelium is atypical & hyperplastic with papillary projections into lumen | Histology

Prostatic intraepithelial neoplasia (PIN)

# Prostate Prognosis of prostatic adenocarcinoma

90% survival for 15 years

# Testis * Failure of testis to complete normal descent into scrotum * Most commonly unilateral, slight predilection for right testis * May result in infertility or germ cell neoplasms

Cryptorchidism | Congenital Anomaly

# Testis Cryptorchidism | Treatment

* Orchiopexy (surgical placement of undescended testis into scrotum) OR * Orchiectomy

# Testis * Occurs in children & young adults * Sudden onset of testicular pain after physical activity * Urological emergency * Surgical correction (detorsion & orchiopexy) required within 6 hours * Otherwise results in swelling, hemorrhagic infarct, and necrosis

Testicular Torsion | Vascular Pathology

# Testis * Incidence: 6/100,000 males * More common in Caucasians than African-Americans | Epidemiology

Testicular tumors

# Testis 1. Cryptorchidism: 3-5x increased risk in undescended testis; increased risk in contralateral decended testis 2. Family Hx: brothers have 8-10x increased risk 3. Intersex syndromes: androgen insensitivity; gonadal dysgenesis | Risk Factors

Testicular tumors

# Testis Types of testicular tumors | Histology

1. Germ cell tumors (GCT): 95% 2. Sex-cord stromal tumors: 5% 3. Lymphoma

# Testis Most common type of testicular tumor

GCT | >95% of cases

# Testis Age: 25-45 yrs | Characteristics of Testicular Tumors

GCT

# Testis Behavior: highly aggressive, but curable | Characteristics of Testicular Tumors

GCT

# Testis Clinical: painless enlargement of testis | Characteristics of Testicular Tumors

GCT

# Testis Genetic abnormalities: isochromosome 12p | Characteristics of Testicular Tumors

GCT

# Testis Treatment: radiation and/or CTX | Characteristics of Testicular Tumors

GCT | 80-90% can be successfullly treated

# Testis Age: prepubertal | Characteristics of Testicular Tumors

Sex-cord stromal tumors

# Testis Behavior: ~90% are benign | Characteristics of Testicular Tumors

Sex-cord stromal tumors

# Testis Most common testicular neoplasm in men age > 60

Lymphoma | DLBCL type

# Testis Most common tumors in men ages 15-40

GCT

# Testis * More common in white population * Most cases are preceded by intratubular neoplasia | Epidemiology

GCT

# Testis * Cryptorchidism: 3-5x increase * Testicular (gonadal) dysgenesis | Risk Factors

GCT

# Testis Painless testicular mass / enlargement | Clinical Presentation

GCT

# Testis Types of GCT | Histology

1. Seminoma: 35-45% 2. Non-seminomatous GCT 3. Mixed GCT: 32-54%

# Testis Prepubertal tumors | Histogenesis

* GCT: endodermal sinus tumor; teratoma * Behavior: usually benign

# Testis Postpubertal tumors | Histogenesis

* 95% of all testicular tumors are GCT * All are malignant

Histology: Testis

* Functional units: seminiferous tubules * Site of spermatogenesis * Contains germ cells & supporting cells * Germ cells: spermatogonia, spermatocytes, spermatids, spermatozoa * Supporting cells: Sertoli cells * Stroma between tubules provides support * Supporting cells: Leydig cells

# Testis GCT composed of mature fetal tissue dervied from 2-3 embryonic layers | GCT Subtypes

Teratoma | Somatic cell lineage

# Testis GCT composed of immature, primitive fetal tissue

Embryonal carcinoma

# Testis GCT that resembles undifferentiated spermatogonia | GCT Subtypes

Seminoma

# Testis GCT that mimics yolk sac elements | GCT subtypes

Endodermal sinus tumor | Extraembryonic cell lineage

# Testis GCT composed of cytotrophoblasts & syncytiotrophoblasts that mimics placental tissue | GCT Subtypes

Choriocarcinoma | Extraembryonic cell lineage

# Testis * 1/3 - 1/2 of all testicular GCT * Most common between ages 15-40 * Hx of cryptorchidism in 10% of cases | Epidemiology

Seminoma

# Testis Clinical: painless testicular swelling Gross: bulky homogenous grey-white lobulated mass * Hemorrhage & necrosis: rare * Usually limited by tunica albuginea | Presentation

Seminoma

# Testis Seminoma | Approach to Therapy

Radiotherapy: high cure rate

# Testis Subtypes of seminomas | Histology

1. Classic type 2. Spermatocytic type

# Testis * Cytology * Large round cell * Distinct membranes * Clear or light cytoplasm * Large central nucleus * Prominent nucleoli * Architecture * Nests or individual tumor cells divided by fibrous bands * Abundant lymphocytes * Possible granulomas * Equivalent to dysgerminoma in women | Histology

Seminoma, classic type

# Testis Seminoma, classic type | Approach to Diagnosis

IHC * Germ cell markers: OCT 3/4, CD117 * CD30- * AFP- * B-hCG+ (15% of cases)

# Testis * Patients age > 50 * Benign, indolent behavior * Size: 2-20 cm (avg. of 7 cm) * Gross: large tumor of myxoid appearance * Exclusive in testicle, usually bilateral | Presentation

Seminoma, spermatocytic type

# Testis * 3 cell types: small, intermediate, large * Numerous mitotic fifures * No lymphocytes, granulomas, or ITGCN | Histology

Seminoma, spermatocytic type

# Testis Seminoma, spermatocytic type | Potential Complications

Sarcomatous transformation: worse prognosis * Rhabdomyosarcoma * Undifferentiated

# Testis Seminoma, spermatocytic type | Approach to Therapy

Surgical treatment only

# Testes Peak occurence in ages 20-30s | Epidemiology

Embryonal carcinoma

# Testis * Aggressive with early hematogenous spread * Often metastatic at time of diagnosis * Most often seen as component of mixed GCT * Gross: fleshy grey-tan tumor often with prominent necrosis & hemorrhage * Often penetrates tunica albuginea | Presentation

Embryonal carcinoma

# Testis * Solid, glandular & papillary growth * Anaplastic cells * Necrosis | Histology

Embryonal carcinoma

# Testis Embryonal carcinoma | Approach to Diagnosis

IHC * B-hCG+ (60% of cases) * CD30+ * Cytokeratin+

# Testis Occurs at any age * Children: pure form; 2nd most common testicular tumor in children * Adult: common component of mixed GCT | Epidemiology

Teratoma

# Testis * Behavior depends on age * Child: benign * Adult: malignant; chemoresistant * Gross: heterogenous collection of differerentiated cells or organoid structures * Solid, cystic, or cartilaginous masses | Presentation

Teratoma

# Testis * Derivates from more than one germ layer * Elements may be mature or immature * Mature: resembling adult tissues * Immature: sharing histologic features with fetal / embryonal tissues * Fibrous or myxoid stroma | Histology

Teratoma

# Testis Germ Layer Derivatives | Histology

* Endoderm * Epithelium lining body tubes (e.g., GI tract) * Parenchyma: endocrine glands, liver * Mesoderm * Supporting tissues: muscles, cartilage, bone * Vascular system * Ectoderm * Nervous tissue * Skin

# Testis * Children: pure form * Most common testicular tumor in children * Very good prognosis * Adults: component of mixed GCT * Most often associated with embryonal carcinoma | Epidemiology

Endodermal sinus tumor

# Testis Endodermal sinus tumor | Approach to Diagnosis

* Serum marker: AFP+ * Histology: * Schiller-Duval bodies (35-50% of cases) * Eosinophilic hyalin globules (AFP) | Schiller-Duval bodies = pathognomonic

# Testis * Various growth patterns: * Reticular (lacelike network) * Microcysts, sheets, tubulo-papillary, etc. * Histological hallmark: Schiller-Duval bodies * Glomeruloid-like structure * Central blood vessel surrounded by loose primitive stroma w/ outer mantle of cuboidal-to-columnar neoplastic cells lined by flattened tumor cells | Histology ## Footnote `

Endodermal sinus tumor

# Testis * Peak occurence in 30s * Rare (<1%); more commonly mixed | Epidemiology

Choriocarcinoma

# Testis * Aggressive tumor; lungs & liver usually involved * Gross: small (<5 cm) palpable masses w/ strikingly hemorrhagic appearance * Often no testicular enlargement * Often presents w/ hematogenous mets | Presentation

Choriocarcinoma | Strikingly hemorrhagic appearanc is characteristic

# Testis Mass composed of cytotrophoblasts & syncytiotrophoblasts | Histology

Choriocarcinoma

# Testis * Small polygonal cell * Single nucleus * Clear / pale cytoplasm * Distinct membranes | Histology

Cytotrophoblasts

# Testis * Large multinucleated cell * Abundant eosinophilic cytoplasm * B-hCG+ | Histology

Syncytiotrophoblasts

# Testis Choriocarcinoma | Approach to Diagnosis

* Clinically: characteristic hemorrhagic appearance * Serum marker: B-hCG * Produced by syncytiotrophoblasts

# Testis Mixed GCT

* Mixed: 2 or more GCT subtypes in same testis * Peak occurence between ages 15-30 * Frequent components: * Embryonal carcinoma * Teratoma * Endodermal sinus tumor * 90% of cases: elevated B-hCG & AFP

# Testis Benign, non-germ cell tumors derived from testicular interstitium | Pathology

Sex cord-stromal tumors

# Testis Types of sex cord-stromal tumors | Histology

1. Leydig cell tumor 2. Sertoli cell tumor

# Testis Testicular mass asssociated with hormonal symptoms: * Precocious puberty * Gynecomastia | Clinical Presentation

Leydig cell tumor | Testosterone is major hormone produced by Leydig cells

# Testis * Patients between ages 20-60 * Testicular mass a/w hormonal symptoms: * Precocious puberty * Gynecomastia | Clinical Presentation

Leydig cell tumor | Testosterone is major hormone produced by Leydig cells

# Testis * Homogenous, solid, well-demarcated, circumscribed nodule * Yellow or brown color | Gross Appearance

Leydig cell tumor

# Testis * Diffuse, nodular growth pattern * Uniform polygonal cells with granular, eosinophilic cytoplasm * Histological hallmark: Reinke crystals (rare)

Leydig cell tumor

# Testis * Testicular mass / small firm nodules * Clinically silent | Clinical Presentation

Sertoli cell tumor

# Testis Neoplastic cells arranged in trabeculae / tubules | Histology

Sertoli cell tumor

# Testis Confined to testis, epididymis, or spermatic cord | Testicular Tumor: Staging

Stage I

# Testis Spread confined to retroperitoneal nodes below diaphragm | Testicular Tumor: Staging

Stage II

# Testis Spread outside of retroperitoneal nodes or above diaphragm | Testicular Tumor: Staging

Stage III

# Testis Testicular Tumors | Approach to Treatment

Radical orchiectomy and/or CTX

# Testis Testicular Tumor | Prognosis

* Seminoma: >95% of patients with localized disease (stage I) or spread to nodes below diaphragm (stage II) can be cured * Non-seminomatous: 90% can enter remission with aggressive treatment

Overview: GU Pathology Flashcards

(113 cards)