Prostate disorders and cancer: Pathology review

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Case Study0:00–1:35

On the urology ward, two people came in. The first is 63-year-old Joseph who complains of difficulty with urination.
More specifically, he says he has trouble initiating his stream of urine, and after urination, his bladder still feels full.
He also wakes up several times each night feeling the need to urinate. These symptoms have been present for the past few years, but have gradually become worse.
Digital rectal examination revealed symmetrically enlarged, smooth, firm, nontender prostate with rubbery or elastic texture.
The second is Sam, a 72-year-old African-American individual who comes in with lower back pain that is not relieved by rest or position changes and has been increasing over the past couple of months.
He has also noticed recent feelings of fatigue and weight loss, which he attributes to decreased appetite. On further history, he consumes a diet low in fiber and high in saturated fat and red meat.
On digital rectal examination, an irregular, hard lump is palpated in the posterior of his prostate. Labs show increased alkaline phosphatase and total PSA levels with decreased free to total PSA ratio.Both Joseph and Sam have different forms of prostate disorders!
Let’s first remind ourselves about physiology real quick. The prostate is a small gland whose job is to secrete an alkaline milky liquid that joins the sperm and the semen.

Physiology1:35–2:04

To do that, it sits under the bladder and in front of the rectum. That’s important because when we do digital rectal exam, we’re able to palpate the posterior of the prostate.
The urethra goes through the prostate before reaching the penis. And that part of the urethra is called the prostatic urethra.
Now, the prostate can be divided into a few zones and this is high yield! The peripheral zone, which is the outermost posterior section, is the largest of the zones and contain about 70% of the prostate’s glandular tissue.

Anatomy2:04–3:23

Moving inward, the central zone contains about 25% of the glandular tissue. Last, is the transitional zone, which contains around 5% of the glandular tissue, and is located in the periurethral region of the prostate.
The transitional zone gets its name because it contains transitional cells which are also found in the bladder. At the microscopic level, the prostate is made up of stroma, or connective tissue, and glands.
Each of these glands is surrounded by a basement membrane and lined by an outer layer of cuboidal basal cells and an inner ring of luminal columnar cells, which are within the lumen or center of the gland.
An important thing to remember is that both the basal cells and luminal cells of the prostate rely on stimulation from androgens for survival, including testosterone which, at the prostate, is converted by the enzyme 5α-reductase into the more potent dihydrotestosterone.
Okay, now, the first prostate disorder is prostatitis or inflammation of the prostate. This can be either acute or chronic.

Prostatitis3:23–4:49

Acute prostatitis is usually due to bacteria. In young adults, that’s most commonly Chlamydia trachomatis and Neisseria gonorrhoea, whereas in older individuals, it’s usually Escherichia coli, followed by Pseudomonas.
Now, acute prostatitis classically presents as dysuria with fever and chills. A particularly high-yield fact for your test is that on a digital rectal exam, the prostate will be warm, tender and boggy.
Also, lab analysis of prostatic secretions will show increased white blood cells and culture will reveal the pathogenic bacteria.
Chronic prostatitis, on the other hand, can be bacterial or nonbacterial, such as secondary to previous infection, nerve problems or chemical irritation.
Similarly to acute prostatitis, it also presents as dysuria, but the key hint here is that the individual is typically afebrile and also complains on pelvic or lower back pain.
On digital rectal examination, the prostate may feel normal, tender, or boggy. Prostatic secretions will again show increased white blood cells, but culture may be negative in nonbacterial cases.Moving on to benign prostatic hyperplasia or BPH for short.

Benign Prostatic Hyperplasia4:49–9:44

This is hyperplasia of both the stroma and the glands of the prostate. For your tests, note that it’s hyperplasia, which is an increase in the number of cells, and not hypertrophy, which would mean an increase in the size of the cells.
It is driven by 5α-reductase activity in the prostate which increases with age, leading to increased dihydrotestosterone production.
Dihydrotestosterone then makes prostate cells live longer and multiply faster. A high yield fact to remember is that this is actually a normal process of aging, and around 50% of men develop BPH by the age of 60.
Another important thing to remember is that BPH is not associated with any increased risk for developing prostate cancer.
Rather, as the prostate gland enlarges, small hyperplastic nodules can form within it. A particularly high-yield fact is that these hyperplastic nodules will typically form in the periurethral region of the prostate.
When these nodules or the prostate tissue itself compress the prostatic urethra, it becomes more difficult for urine to pass though, leading to a weak and inconsistent stream of urine, called dribbling.
Since the prostate sits just below the bladder, when it’s enlarged, it can cause bladder outflow obstruction. Also the person might have to strain when urinating to overcome the obstruction, have pain during urination called dysuria, or trouble initiating and stopping urination called hesitancy.
So the urine builds up in the bladder causing it to dilate, creating a constant sense of incomplete bladder emptying and overflow incontinence.
In response, the smooth muscle walls of the bladder will contract harder, and this leads to bladder hypertrophy were the walls thicken and become irritable.
This increases the frequency of urination at night, which is called nocturia. Now, one complication of the stagnation of urine in the bladder is that it promotes bacterial growth, and can lead to urinary tract infections.
Also, the urine can build up back into the ureter and the kidney, causing hydronephrosis, or dilation of the renal pelvis and calyces.
Severe long-standing hydronephrosis can subsequently compress the renal parenchyma, resulting in atrophy of the renal medulla and cortex.Diagnosis of BPH starts with digital rectal examination.
What’s high-yield here is that the prostate will be symmetrically enlarged, smooth, firm, nontender with rubbery or elastic texture.
Levels of prostate specific antigen or PSA, a substance produced by healthy prostate cells, will be also elevated, since there are more cells around making the PSA.
However, that’s not specific for BPH and can be true for a handful of other prostate disorders.Treatment of BPH focuses on relieving the obstruction and allowing the urine to flow normally.
This can be done through medications like finasteride, a 5α-reductase inhibitor. For your test, remember that 5α-reductase inhibitors shrink the prostate gland by inhibiting the conversion of testosterone into dihydrotestosterone.
Another high-yield fact to keep in mind is that it can take up to 6-12 months for symptom improvement and side effects include decreased libido and erectile dysfunction.
Next, α1-antagonists like terazosin and tamsulosin can bind to α1 receptors on the smooth muscles in the neck of the bladder, the prostate, and urethra, causing them to relax and allowing urine to pass.
These are usually preferred for symptom improvement within days to weeks. Side effects include orthostatic hypotension and dizziness.
Another type of smooth-muscle relaxants is antimuscarinics, like tolterodine or oxybutynin. These are especially useful for those with irritable bladder symptoms.
For your test, remember that they are avoided in individuals with increased post-void residual volume, which is the volume of urine retained in the bladder after a voluntary void.
This is because relaxing the bladder can increase the urinary retention even more. Next, phosphodiesterase type 5, or PDE5 inhibitors like tadalafil can be also used, especially in individuals with concurrent erectile dysfunction.
In some cases, surgical procedures like ablation or transurethral resection of the prostate, or TURP, can be done to remove part or all of the prostate.Alright, now, the next prostate disorder is prostatic adenocarcinoma.
A high yield epidemiology fact to remember is that this is the most common cancer and the second most common cause of cancer death in males.
Risk factors include age older than 50 and if the person is of African descent. An extremely high-yield fact you should absolutely remember is that prostate adenocarcinoma most commonly occurs in the posterior peripheral zone of the prostate.

Prostatic Adenocarcinoma9:44–14:33

The reason why that’s so important is that it is actually far away from the urethra. As a result, these tumors can grow quite large before they cause problems with urination.
Over time, if the cancer does compress or invade the urethra or bladder, it can cause difficulty urinating, bleeding, and pain with urination and ejaculation.
If the cancer becomes metastatic, it most commonly spreads via the vertebral venous plexus, also called Batson plexus, to the bones of the axial skeleton, like the vertebrae or pelvis, resulting in hip or lower back pain.
The key symptom here to differentiate it from benign causes of back pain is that it gets worse at night and not relieved by rest or position change.
A high-yield fact to know is that these metastatic lesions are osteoblastic or sclerotic, rather than lytic ones.For diagnosis, on digital rectal examination, the tumor can be easily palpated in the posterior of the prostate and feel like an irregularly hard lump.
Prostate cancer can also cause elevation in certain tumor markers like prostatic acid phosphatase, or PAP for short, and PSA.
Since PSA elevation is non-specific, what helps determine the risk of cancer is calculating the free to total PSA ratio.
Specifically, PSA circulates in the serum in two ways: either on its own, called free PSA, or bound to other proteins. For unclear reasons, the lower the free to total PSA ratio, the higher the risk of cancer and the greater the necessity of a prostate biopsy.
Now, in a biopsy of prostate adenocarcinoma, what we would classically see are small glands that infiltrate the normal prostatic tissue.
A characteristic finding is that the nuclei of the tumor cells have dark nucleoli. Based on the architecture of the tumor cells, the tumor can then be scored using the Gleason grading system.
The Gleason scale identifies the two most common architecture patterns within the prostate tissue and assigns a score between one and five to both of them.
A score of 1 represents normal, well differentiated cells, and a score of 5 represents highly abnormal cells that barely resemble the normal prostate tissue.
Once the primary and secondary patterns have each received a score from one to five, these two numbers are added together, resulting in a total Gleason score between two and 10 with two representing low-grade tumors and 10 representing high-grade, dangerous tumors.
Now, regarding metastatic disease, radionuclide bone scanning can be also done to look for bone lesions. A high yield fact to remember is that If these are present, serum alkaline phosphatase will be elevated as well, and this can be a useful screening tool for recurrent bone metastasis.
In terms of treatment, when the tumor is confined to the prostate, and hasn’t metastasized, surgical excision of the prostate, also known as prostatectomy, is done along with radiotherapy and hormonal therapy.
Now, the most commonly tested medications used in hormonal therapy are leuprolide and flutamide. Leuprolide is a gonadotropin-releasing hormone or GnRH analog that when administered in continuous fashion, results in downregulation of GnRH receptors in the pituitary, which then reduces LH and FSH secretion, both of which promote androgen secretion and the growth of prostate cancer cells.
Flutamide is an androgen receptor antagonist. So both leuprolide and flutamide deprive cancer cells of androgen stimulation.
Sometimes older individuals with low stage non-metastatic prostate cancer might decide to undergo active surveillance instead since prostatectomy can cause certain complications, like damaging the prostatic plexus, resulting in erectile dysfunction.
If the tumor has metastasized however, treatment options include radiation therapy, chemotherapy, and hormonal therapy. All right, as a quick recap, prostatitis can be acute, which is usually caused by bacteria, and causes fever and dysuria, or chronic, which can be bacterial or non-bacterial, and causes dysuria and back pain.
Benign prostatic hyperplasia is a normal phenomenon in individuals older than 50 and does not increase the risk for cancer.
It manifests as a smooth, elastic, firm nodular enlargement in the periurethral zone of the prostate. Classic presentation include dribbling, dysuria, hesitancy, increased frequency of urination and nocturia.

Review14:33–15:43

Complications include UTI’s and hydronephrosis. Prostatic adenocarcinoma typically develops as an irregular hard lump in the posterior peripheral zone of the prostate.
It can be asymptomatic or present with back pain later on due to bone metastases. Tumor markers include PAP and PSA.
If bone metastasis occurs, serum alkaline phosphatase will be elevated. Finally, the diagnosis needs to be confirmed with a biopsy.Now, let’s not forget about our cases!
63-year-old Joseph has the classic symptoms of benign prostate hyperplasia: straining on urination, hesitancy and nocturia.
The key finding to point us towards BPH is a symmetrically enlarged, smooth, firm and nontender prostate on digital rectal examination.
This is disorder is particularly common for his age. He got started on finasteride and now he is doing much better!
Regarding 72-year-old Sam, he came in with low back pain not relieved with rest or posture changes, as well as fatigue, anorexia and weight loss.

Summary15:43–17:02

On digital rectal examination, an irregular hard lump was palpated in the posterior prostate. This along with the increased alkaline phosphatase and PSA levels and decreased free to total PSA ratio is characteristic for bone metastasis from prostatic adenocarcinoma.
Other clues include his age, African-American descent, and low fiber diet, which are all risk factors for the development of prostate adenocarcinoma.
The diagnosis was confirmed with a prostate biopsy and a radionuclide bone scan showing spine metastasis. He started receiving hormonal therapy, specifically leuprolide.
alkaline phosphatase and psa levels and decreased free to total psa ratio is characteristic for bone metastasis for prostatic adenocarcinoma Other clues include his age African American descent and low fiber diet which are all risk factors for the development of prostate adenocarcinoma The diagnosis was confirmed with a prostate biopsy and a radionuclide bone scan showing spine metastasis He started receiving hormonal therapy specifically