LECTURE NOT FIRST AID - Male Repro Path Flashcards
What are the symptoms that present with urinary cystitis?
Dysuria, frequency, urgency, and suprapubic pain
What lab values will we see in someone with urinary bladder cystitis?
- Cloudy UA with more than 10 WBCs/HPF
- Dip: + leukocyte esterase and nitrites (bacteria convert nitrates to nitrites)
- Culture - >100K CFU (gold standard)
What are the acute causes of urinary bladder cystitis and how might we distinguish them?
- E.Coli (80%)
- Staph Saphrophyticus particularly in young sexually active women
- Klebsiella pneumoniae
- Proteus mirabilis - Alkaline urine with a scent of ammonia
- Enterococcus faecalis
In a subacute inflammation of the urinary bladder, what will we see under the microscope?
Lots of eosinophils
In chronic urinary bladder cystitis, what causes it?
- Certain bacteria can
- Schistosoma haematobium (Think Egypt and Sudan)
What will see in an inflammed urinary bladder wall if the cause is a chronic bacterial infection?
- Malacoplakia (large yellow plaques
- foamy macrophages
- Michaelis-Gutmann bodies (which are deposition of Ca in lysosomes)
What can cause hemorrhagic urinary bladder inflammation?
- Cyclophosphamide
- Adenovirus
Urothelial tumors of the bladder, as you might expect, are transitional cell based. They are the most common type of lower urinary tract cancer.
What risk factors are there for these?
- Smoking (PAH)
- Naphthylamine
- azo dyes/aryl amines (watch out hairdressers)
- long term use of analgesics, cyclophosphamide or phenacetin
- Being an old fart
- Irradiation
If someone has urothelial transitional cell tumors, how will they present?
Painless hematuria
What mutations cause urothelial transitional cell tumors?
- FGFR3
- RAS
- p53
- RB
Discuss low vs high grade process for genetic involvement of urothelial transition cell tumors
- High grade = Flat (in situ) - Invades, p53 mutations
- Low grade to high grade = Papillary = Invades superficially, chromosome 9 mutation/deletion, p16 (INK4a), invasive 17p deletion and p53
How do we treat urothelial transitional cell tumors?
Surgery, but tumors are multifocal and can recur, we call this the “field defect”
This type of urinary bladder cancer is invasive and fungating
Mixed (urothelial AND squamos)
What is squamos cell carcinoma of the urinary bladder associated with?
- Schistosoma hematobium (Egypt)
- Cystitis
- Chronic nephrolithiasis
What is the etiology behind squamos cell carcinoma of the urinary bladder?
Chronic bladder infection/irritation causes squamos metaplasia
What is adenocarcinoma of the bladder and what is it associated with
This is a rare, malignant proliferation of glands associated with intestinal metaplasia
What structural defects are associated with adenocarcinoma of the urinary bladder?
- Urachal remnant (tumor develops at the dome of the bladder)
- Cystitis glandularis
- Exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls)
What are the two types of mesenchymal tumors we find in the urinary bladder?
Leiomyoma - Benign encapsulated mass
Leiomyosarcoma - Malignant
In males and females we can get obstructions of the urinary bladder. What are they and what do they look like on histology?
- Male - Prostate hyperplasia
- Female - Cystocele
Hypertrophy, trabeculation of the wall which leads to crypt formation
What symptoms accompany Urethritis?
Dysuria, itching, and increased urinary frequency
What causes urethritis?
Chlamydia Trachomatis
Neisseria Gonorrhea
Mycoplasma
What specific lab and culture will we see with urethritis?
Sterile pyuria with more than 10 WBCs/hpf and leukocyte esterase with a NEGATIVE urine culture
What is a hypospadias and what causes it?
- Opening on inferior surface
- Failure of the urethral folds to close
What is Epispadias and what causes it?
- Opening on the superior surface
- Caused by abnormal positioning of the genital tubercle
What is a Phimosis and what causes it?
- Foreskin cannot be retracted over the glans. Can just occur or be related to balanitis/glans inflamm
What is Balanoposthitis and what tends to cause it?
Infection of glans and prepuce caused by C. Albicans, Gardnerella and bacteria
What tends to cause Balanoposthitis?
- Poor hygiene
- Uncircumsized penis
- SMEGMA (Renuka’s favorite)
What is/what causes Lymphogranuloma Verenum?
This is an STD causes by Chlamydia Trachomitis, serotypes L1-L3
What is the progression of Lymphogranuloma Verenum?
This is a necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes that eventually heals with fibrosis, although perianal involvement may result in rectal sticture
What is and what causes Condylmoa Acuminatum?
This is a benign warty growth on genital skin caused by HPV 6 or 11
For Condyloma Acuminatum, what do we see under histology?
We see villous, papillary connective tissue stroma covered by epithelium, hyperkeratosis and acanthosis with koilocytosis (cytoplasmic vacuolization of squamos cells)
What is Verrucous Carcinoma?
Well differentiated, benign, squamos cell carcinoma with low malignant potential
What causes/ what is Bowen Disease?
This is a squamos cell carcinoma of the penile shaft or scrotum that presents as leukoplakia due to HPV 16
What do we see under histology for Bowen Disease?
Proliferation of Epidermis with mitoses, and some dysplasia with hyperchromatic nuclei.
An intact BM allows for a sharp dermal-epidermal border
What are the three carcinomas (in situ) of the penis, and which one (ones) progresses to an invasive carcinoma?
- Bowen disease
- Erythroplasia of Queyrat
Both of those can progress to invasive carcinoma, but the third, Bowenoid papulosis, does not progress to invasive carcinoma
What is Erythroplasia of Queyrat and how does it present?
Like Bowen disease, it is a squamos cell carcinoma, however, this one presents as an erythroplakia
What is Bowenoid papulosis?
The final squamos cell carcinoma of the penis, this presents with multiple redish purple papules in folks less than 40.
What predisposes someone to a malignant squamos cell carcinoma of the penis?
- HPV types 16, 18
- Not being circumcised (foreskin + poor hygiene = inflammation and irritation)
What are the two types of malignant squamos cell carcinoma of the penis?
- Papillary -Simulate condylomata Acuminata; cauliflower-like fungating mass
- Flat - Epithelial thickening with graying and fissuring of the mucosal surface
What is and what leads to cryptorchidism?
This is failure of the testicle to descend into the scrotal sac due to a problem with phase 2 of descent (inguinoscrotal to transabdominal phase).
This occurs in 1% of male infants
What are the complications of cryptorchidism and what can we do to fix it?
Complications include testicular atrophy, infertility, seminoma, inguinal hernia
Most resolve spontaneously, an orchipexy can be done before the age of 2 years
Regressive atrophy of the testis and epididymis can occur in the setting of a wide array of conditions from irradiation to hypopituitarism. But what morphology does this degeneration take on?
Hyalinization and thickening of the BM of spermatic tubules.
LEYDIG CELLS ARE SPARED
What is orchitis and what physical exam test can help us distinguish it from an inflammed epididymis?
Orchitis is inflammation of the testicles. Like epididymis swelling it can be asymptomatic or have scrotal pain, but unlike epididymis, which has an intact cremasteric reflex, orchitis loses the cremasteric muscle contraction when you rub the inner thigh
What are the causes of orchitis (8 causes)?
- Chlamydia trachomatis (serotypes D-K)
- N. gonorrhea - Occurs in young adults - Labido is unaffected due to Leydig cells being spared but can cause infertility
- E. Coli and Pseudomonas - Common in older adults and UTIs
- Mumps virus - Teenagers with parotid swelling, causing infertility
- TB, which will hit the epididymis and testis
- Syphilis - Just hits the testis, leading to diffuse inflammation with edema, lymphocytes and plasma cells
- Granulomatous from autoimmune
What causes testicular torsion and how does it present?
Congenital failure of the testes to attach to the inner lining of the scrotum (via the processus vaginalis). Can also be due to infections and trauma.
Patients will have very sudden pain and a loss of their cremasteric reflex.
Does testicular torsion involve a venous or arterial circulation cut off?
Cutoff venous drainage with twisting of the spermatic cord. In 6 hours you’ll have necrosis.
What is a Varicocele? How does it present?
Dilation of the spermatic cord with a venous drainage cutoff, leading to a urologic emergency.
It presents as scrotal swelling with a “bag of worms” appearence
What side is the varicocele usually on?
Usually left sided; L testicular vein drains –> left renal vein, while the R testicular vein goes straight to the IVC. The extra path predisposes this side to backup.
What is a hydrocele and how does it come about? What do we see on exam?
Fluid collection in tunica vaginalis
Caused by incomplete closure of the processus vaginalis, stopping communication w/peritoneal cavity (infants) or blockage of lymph drainage (adults)
Sx: scrotal swelling that can be transilluminated
What is the most common spermatic cord tumor? Who is at rick for it?
Giant cell tumor is the most common tumor of the spermatic cord
Risk factors:
- 15 - 40yo
- cryptorchidism
- Klinefelter syndrome
- white >black (5:1)
- Testicular dysgenesis syndrome
What is the pathogenesis of giant cell tumors of the spermatic cord?
originate from intratubular germ cell neoplasia (ITGCN)
OCT3/4 & NANOG transcription factors assoc w/pluripotentiality
Discuss the histology of a seminoma vs a nonseminoma
Seminoma - large cells w/ clear cytoplasm and central nuclei w/1-2 prominent nucleoli (resemble spermatogonia); homogeneous mass w/NO hemorrhage or necrosis
Nonseminomas tend to not be homogenous and have either hemorrhage or necrosis
What mutation causes Seminoma?
isochromosome 12p; 2 c-KIT activating mutations
Describe the clinical path of Seminoma. How does it present? In whom? Whats the prognosis? How do we deal with it?
Clinical: 20-30yo, Rare cases may produce β-hCG.
Tx: highly responsive to radiotherapy
Prognosis: excellent, metastasize late
What is a spermatic seminoma? How does it present?
Uncommon tumor
At risk: >65 yo
Prognosis: excellent -Slow growing, no mets
Histo: Small, medium & large cells
What is an embryonal carcinoma and what is its morphology?
malignant tumor of immature, primitive cells
May produce glands; forms a hemorrhagic mass w/ necrosis
Aggressive w/ early hematogenous spread
Why is treatment for embryonal carcinoma dangerous?
Chemotherapy may cause differentiation into another type of germ cell tumor (e.g., teratoma)
What mutation is associated with embryonal carcinoma?
- OCT 3/4
- PLAP
- cytokeratin
- CD30 (C-KIT neg)
What labs do we associate with embryonal carcinoma?
Remember this guy is from primitive undifferentiated cells, so it can release AFP or B-HCG
What is the most common child testicular tumor and what presentation does it give clinically and histologically?
Yolk Sac tumor
Histo: resembles yolk sac elements; Schiller-Duval bodies (glomerulus-like/false yolk sac)
We see an increased AFP with this tumor in the clinic
What causes a choriocarcinoma?
malignant tumor of syncytiotrophoblasts (produce β-hCG) and cytotrophoblasts (placenta-like tissue, but villi are absent)
Spreads early via blood
Patho: inc β-hCG =
hyperthyroidism or gynecomastia (a-subunit of hCG is similar to that of FSH, LH, and TSH)
Presentation of choriocarcinoma
We won’t see any testicular enlargement, but there will be a small palpable nodule less than 5cm
What testicular tumor presents with both increased AFP and b-HCG? What is it?
Teratoma
mature fetal tissue derived from 2+ embryonic layers.
What is the clinical presentation and histology of a leydig cell tumor?
usually produces androgen, causing precocious puberty in children or gynecomastia in adults
Histo: Reinke crystals (rod-like cytoplasmic inclusions)
Most common testicular mass in males > 60 years old
often bilateral
Testicular Lymphoma
What type of histology do we see with Testicular lymphomas?
Histo: diffuse large B-cell Type
(+) CD45 (LCA), CD20
What bacteria cause prostatitis in young adults? Older?
- young adults: Chlamydia trachomatis & Neisseria gonorrhoeae
- older adults: E. coli & Pseudomonas
Symptoms of acute vs chronic prostatitis
Acute Sx: Dysuria, fever, chills; tender & boggy on DRE
Chronic Sx: dysuria, pelvic/ low back pain
Labs for acute vs chronic prostatitis
Acute labs: Prostatic secretions= WBCs; culture= bacteria
Chronic labs: Prostatic secretions= WBCs; culture= (-)
Describe the pathogenesis of Benign Prostatic Hyperplasia
central periurethral zone: Testosterone--> (5a-reductase in stromal cells) to DHT, which binds to androgen receptor of stromal and epithelial cells leading to androgen-dependent gene activation of: - FGF-7 - FGF1,2 - TGFB
Symptoms of BPH?
Sx: Problems starting and stopping; Dribbling, Impaired bladder emptying, hematuria
What treatments do we have for BPH?
-α1-antagonist (terazosin,tamsulosin) =relax smooth muscle, lower BP
-5α-reductase inhibitor= Blocks testosterone–>DHT
Side effects=gynecomastia and sexual dysfunction.
-Transurethral Resection of Prostate (TURP) = gold standard
Most common cancer in men and how it presents
Adenocarcinoma of the prostate
Sx: most tumors in peripheral zone, posterior region of the prostate= no urinary symptoms
What risk factors do we have for adenocarcinoma of the prostate?
Risk factors: age, African > Caucasians> Asians (shorter CAG repeats on X-linked AR gene), diet high in saturated fats
What labs do we see for prostate adenocarcinoma?
Labs: high PSA (>10 ng/dL), dec %free-PSA (cancer makes bound PSA).
What mutations are associated with prostate adenocarcinoma?
mutation: AR - inc P1-3 kinase/AKT (late) - BRCA2 - 8q24 in afr. Amer.
ETS transcription factor juxtaposed to androgen-regulated TMPRSS2 promoter; hypermethylation of GSTP1
Histology of adenocarcinoma of the prostate
Histo: small, invasive glands w/ prominent nucleoli
What can adenocarcinoma of the prostate lead to?
Can lead to osteoblastic metastases (Spread to lumbar spine or pelvis)
Treatment for adenocarcinoma of the prostate
- Prostatectomy
- hormone suppression to reduce testosterone and DHT
- Continuous GnRH analogs (leuprolide) shut down the hypothalamus (LH and FSH are reduced)
- Flutamide =competitive inhibitor at the androgen receptor.
This benign precursor lesion on histology has acini lined by cytologically atypical cells w/prominent nucleoli
Prostatic Intraepithelial Neoplasia (PIN)
