Prostatitis: Causes, Symptoms, Diagnosis & Treatment

Prostatitis

Inflammation of the prostate or prostatitis may be acute, chronic and granulomatous types. Acute or chronic prostatitis may superimpose on nodular hyperplasia.

Acute Prostatitis

• Acute focal or diffuse suppurative inflammation of the prostate is not uncommon.
• It occurs most commonly due to the ascent of bacteria from the urethra, less often by descent from the upper urinary tract or bladder, and occasionally by lymphomatous or haematogenous spread from a distant focus of infection.
• The infection may occur spontaneously or may be a complication of urethral manipulation such as by catheterisation, cystoscopy, urethral dilatation and surgical procedures on the prostate.
• The common pathogens are those which cause UTI, most frequently E. coli, and others such as Klebsiella, Proteus, Pseudomonas, Enterobacter, gonococci, staphylococci and streptococci.
• The diagnosis is made by culture of urine specimen.

Read And Learn More: Systemic Pathology Notes

Morphologic Features Grossly, the prostate is enlarged, swollen and tense. The cut section shows multiple abscesses and foci of necrosis.

Histologically, the prostatic acini are dilated and filled with neutrophilic exudate. There may be diffuse acute inflammatory infiltrate. Oedema, hyperaemia and foci of necrosis frequently accompany acute inflammatory involvement.

Chronic Prostatitis

• Chronic prostatitis is more common and foci of chronic inflammation are frequently present in the prostate of men above 40 years of age. Chronic prostatitis is usually asymptomatic but may cause allergic reactions, iritis, neuritis or arthritis.
• Chronic prostatitis is of 2 types bacterial and abacterial.
• Chronic bacterial prostatitis is caused in much the same way and by the same organisms as acute prostatitis. It is generally a consequence of recurrent UTIs.
• Diagnosis is made by detection of more than 10-12 leucocytes per high power field in expressed prostatic secretions, and by positive culture of urine specimen and prostatic secretions.
• This condition is more difficult to treat since antibiotics penetrate the prostate poorly.
• Chronic abacterial prostatitis is more common. There is no history of recurrent UTI and culture of urine and prostatic secretions is always negative, though leucocytosis is demonstrable in prostatic secretions.
• The pathogens implicated are Chlamydia trachomatis and Ureaplasma urealyticum.

Morphologic Features: Pathologic changes in both bacterial and abacterial prostatitis are similar.

Grossly, the prostate may be enlarged, fibrosed and shrunken.

• Histologically, the diagnosis of chronic prostatitis is made by foci of lymphocytes, plasma cells, macrophages and neutrophils within the prostatic substance.
• Corpora amylacea, prostatic calculi and foci of squamous metaplasia in the prostatic acini may accompany inflammatory changes. Seminal vesicles are invariably involved.

Granulomatous Prostatitis:

Granulomatous prostatitis is a variety of chronic prostatitis, probably caused by leakage of prostatic secretions into the tissue or could be of autoimmune origin.

Morphologic Features Grossly, the gland is firm to hard, giving the clinical impression of prostatic carcinoma on rectal examination. Histologically, the inflammatory reaction consists of macrophages, lymphocytes, plasma cells
and some multinucleate giant cells. The condition may be confused with tuberculous prostatitis.

Nodular Hyperplasia

• Non-neoplastic tumour-like enlargement of the prostate, commonly termed benign nodular hyperplasia (BNH) or benign enlargement of the prostate (BEP), is a very common condition in men and is considered by some as a normal ageing process.
• It becomes increasingly more frequent above the age of 50 years and its incidence approaches 75-80% in men above 80 years.
• However, symptomatic BEP-producing urinary tract obstruction requiring surgical treatment occurs in
  5-10% of cases only. ETIOLOGY The cause of BEP has not been fully established.
• However, a few etiologic factors such as endocrinologic, racial, inflammation and arteriosclerosis have been implicated but the endocrine basis for hyperplasia has been more fully investigated and considered a strong possibility in its genesis.
• It has been found that both sexes elaborate on androgen and oestrogen, though the level of androgen is high in males and that of oestrogen is high in females.
• With advancing age, there is a decline in the level of androgen and a corresponding rise of oestrogen in males.
• The periurethral inner prostate which is primarily involved in BEP is responsive to the rising level of oestrogen, whereas the outer prostate which is mainly involved in the carcinoma is responsive to androgen.
• A plausible hypothesis suggested is that there is synergistic stimulation of the prostate by both hormones the oestrogen acting to sensitise the prostatic tissue to the growth promoting effect of dihydroxy-testosterone derived from plasma testosterone.

Morphologic Features Grossly, the enlarged prostate is nodular, smooth and firm and weighs 2-4 times its normal weight and may weigh up to 40-80 gm.

• The appearance of the cut section varies depending upon whether the hyperplasia is predominantly of the glandular or fibromuscular tissue.
• In primarily glandular BEP, the tissue is yellow-pink, soft, honey-combed, and milky fluid exudes, whereas in mainly fibromuscular BEP the cut surface is firm, homogeneous and does not exude milky fluid.
• The hyperplastic nodule forms a mass mainly in the inner periurethral prostatic gland so that the surrounding prostatic tissue forms a false capsule which enables the surgeon to enucleate the nodular masses.
• The left-over peripheral prostatic tissue may sometimes undergo recurrent nodular enlargement or may develop carcinoma later.

Histologically, in every case, there is hyperplasia of all three tissue elements in varying proportions glandular, fibrous and muscular.

• Glandular hyperplasia predominates in most cases and is identified by exaggerated intraocular papillary infoldings with delicate fibrovascular cores.
• The lining epithelium is two layered the inner tall columnar mucus-secreting with poorly-defined borders, and the outer cuboidal to flattened epithelium with basal nuclei.
• Fibromuscular hyperplasia when present as the dominant component appears as aggregates of spindle cells forming an appearance akin to fibromyoma of the uterus.
• In addition to glandular and/or fibromuscular hyperplasia, other histologic features frequently found include foci of lymphocytic aggregates, small areas of infarction, corpora amylacea and foci of squamous metaplasia.

Clinical Features Clinically, the symptomatic cases develop symptoms due to complications such as urethral obstruction and secondary effects on the bladder (for example hypertrophy, cystitis), ureter (for example hydroureter) and kidneys (for example hydronephrosis).

The presenting features include frequency, nocturia, difficulty in micturition, pain, haematuria and sometimes, the patients present with acute retention of urine requiring immediate catheterisation.

Carcinoma Of Prostate

Worldwide prostate cancer is the second most common form of cancer in men. It is a disease of men above the age of 50 years and its prevalence increases with increasing age so that more than 50% of men 80 years old have asymptomatic (latent) carcinoma of the prostate.

Many times, carcinoma of the prostate is small and detected as microscopic foci in a prostate removed for BEP or found incidentally at autopsy.

Thus, it is common to classify carcinoma of the prostate into the following 4 types:

• Latent carcinoma This is found unexpectedly as a small focus of carcinoma in the prostate during autopsy studies in men dying of other causes. Its incidence in autopsies has been variously reported as 25-35%.
• Incidental carcinoma About 15-20% of prostatectomies done for BEP reveal incidental carcinoma of the prostate.
• Occult carcinoma This is the type in which the patient has no symptoms of prostatic carcinoma but shows evidence of metastases on clinical examination and investigations.

• Clinical carcinoma Clinical prostatic carcinoma is the type detected by rectal examination and other investigations and confirmed by pathologic examination of a biopsy of the prostate.

Etiology The cause of prostatic cancer remains obscure. However, a few factors have been suspected. These are as under:

1. Endocrinologic factors Androgens are considered essential for the development and maintenance of prostatic epithelium. But how androgens are responsible for causing malignant transformation is not yet clear.
   • However, the etiologic role of androgens is supported by the following indirect evidence:
   • Orchiectomy causes the arrest of metastatic prostatic cancer disease (the testis being the main source of testosterone).
   • Administration of oestrogen causes regression of prostatic carcinoma.
   • Cancer of the prostate is extremely rare in eunuchs and in patients with Klinefelter’s syndrome.
   • Cancer of the prostate begins at the stage of life when androgen levels are high. However, cancer may remain latent with a decline in androgen levels with advancing age.
2. Racial and geographic influences There are some racial and geographic differences in the incidence of prostatic cancer.
   • It is uncommon in Japanese and Chinese, while the prevalence is high in Americans.
   • African Americans have a markedly higher incidence as compared to whites which may be related to genetic variation in the androgen receptor gene.
3. Environmental influences Some common environmental factors and carcinogens have been identified with a high risk of the development of prostatic cancer.
   • These include high dietary fat and exposure to polycyclic aromatic hydrocarbons. Flavonoids, antioxidants and selenium may reduce the risk.
4. Nodular hyperplasia Though nodular prostatic hyperplasia has been suggested by some as a precursor for the development of prostatic cancer, it is considered unlikely.
   • Most prostatic cancers develop in the periphery of the gland while BEP occurs in the periurethral part of the gland. Any concomitant occurrence of the two diseases may be considered an ageing process.
   • Approximately 15-20% of nodular hyperplastic prostates harbour carcinoma.
5. Heredity The possibility of inherited polymorphism of prostatic cancer has been suggested by the observations of familial clustering and 2-fold higher frequency in first-degree relatives.
   • Men with prostate cancer susceptibility gene, BRCA2, have a 20-times increased risk of prostatic cancer.

Histogenesis of prostatic adenocarcinoma has been documented as a multistep process arising from the premalignant stage of prostatic intraepithelial neoplasia (PIN).

• PIN refers to multiple foci of cytologically atypical luminal cells overlying a diminished number of basal cells in prostatic ducts and is a forerunner of invasive prostatic carcinoma.
• Based on cellular atypia, the PIN may be low-grade to high-grade. PIN of high-grade progresses to prostatic adenocarcinoma.
• At the molecular level, the following epigenetic phenomena and acquired somatic mutations have been reported in the development of prostatic cancer:

1. 1. Epigenetic phenomenon Hypermethylation of GSTP1 (glutathione 5-transferase) gene promoter causing loss of function of the gene that detoxifies carcinogens.
   2. Somatic mutation Gene rearrangement in the coding sequence of the ETS family of transcription factor gene that places the mutated gene close to the TMPRSS2 promoter gene, resulting in formation of TMPRSS2-ETS fusion gene in prostatic cancer (TMPRSS2 gene = transmembrane protease serine 2 genes; ETS = E26 transformation specific).

Morphologic Features Grossly, the prostate may be enlarged, normal in size or smaller than normal. In 95% of cases, prostatic carcinoma is located in the peripheral zone, especially in the posterior lobe.

The malignant prostate is firm and fibrous. The Cut section is homogeneous and contains irregular yellowish areas.

Microscopically, as per the 2016 WHO classification, various histologic types of prostatic cancer are described. However, the most common are epithelial tumours.

• Amongst them, acinar adenocarcinoma is the most frequent type; its other variants are atrophic, microcystic, mucinous, signet-ring, sarcomatoid and pleomorphic giant cell type.
• Other less common prostatic cancers are urothelial carcinoma, squamous cell carcinoma, neuroendocrine tumours,
  and rarely sarcomas and malignant lymphomas.
• These rare tumours resemble in morphology with similar malignant tumours elsewhere in the body.
• Prostatic adenocarcinoma is seen in 96% of cases and is generally referred to as carcinoma of the prostate. Its histologic characteristics are as under:
• Architectural disturbance In contrast to the convoluted appearance of the glands seen in normal and hyperplastic prostate, there is a loss of intra-acinar papillary convolutions.
  • The groups of acini are either closely packed in a back-to-back arrangement without intervening stroma or are haphazardly distributed.
• Stroma Normally, a fibromuscular sling surrounds the acini, whereas malignant acini have little or no stroma between them. The tumour cells may penetrate and replace the fibromuscular stroma.
• Gland pattern Most frequently, the glands in well-differentiated prostatic adenocarcinoma are small or medium-sized, lined by a single layer of cuboidal or low columnar cells.
  • Moderately-differentiated tumours have a cribriform or fenestrated glandular appearance. Poorly-differentiated tumours have little or no glandular arrangement but instead, show solid or trabecular patterns.
• Tumour cells The outer basal layer seen in the normal or benign acini is lost. The tumour cells may be clear, dark and eosinophilic cells.
  • Clear cells have foamy cytoplasm, dark cells have homogeneous basophilic cytoplasm, and eosinophilic cells have granular cytoplasm. The cells may show varying degrees of anaplasia and nuclear atypia but are generally slight.
• Invasion One of the important diagnostic features of malignancy in the prostate is the early and frequent occurrence of invasion of intra-prostatic perineural spaces. Lymphatic and vascular invasions may be present but are difficult to detect.

Spread The tumour spreads within the gland by direct extension, and to distant sites by blood and lymphatic route.

Direct spread Direct extension of the tumour occurs into the prostatic capsule and beyond.

In the late stage, the tumour may extend into the bladder neck, seminal vesicles, trigone and ureteral openings.

Metastases Distant spread occurs by both lymphatic and haematogenous routes.

• The rich lymphatic network surrounding the prostate is the main mode of spread to the sacral, iliac and para-aortic lymph nodes.
• The earliest metastasis occurs in the obturator lymph node.
• Haematogenous spread leads most often to characteristic osteoblastic osseous metastases, especially to the pelvis, and lumbar spine other sites of metastases are the lungs, kidneys, and brain.
• The route of blood-borne metastases may be retrograde spread by prostatic venous plexus or via systemic circulation.

Clinical Features And Diagnosis In symptomatic cases, clinical features are urinary obstruction with dysuria, frequency, retention of urine, haematuria, and in 10% of cases pain in the back due to skeletal metastases.

By the time symptoms appear, the carcinoma of the prostate is usually palpable on digital rectal examination (DRE) as a hard and nodular gland fixed to the surrounding tissues.

Two biochemical serum tumour markers employed for diagnosis and monitoring the prognosis of prostatic carcinoma are as under:

1. Prostatic acid phosphatase (PAP) is secreted by prostatic epithelium. Elevation of serum level of PAP is found in cases of prostatic cancer which have extended beyond the capsule or have metastasised. PAP can also be demonstrated in normal prostatic tissues.
2. Prostate-specific antigen (PSA) can be detected by the immunohistochemical method in the malignant prostatic epithelium but is more commonly determined in the serum.

• • The commonly used cut-off value for advising prostate biopsy is serum PSA ≥4 ng/ml (normal 0-4 ng/ml). A reading between 4 and 10 ng/ml is highly suspicious (10% risk) but a value above 10 is quite suggestive of prostatic carcinoma.
  • PSA assay is also helpful in distinguishing high-grade prostatic cancer from urothelial carcinoma, colonic carcinoma, lymphoma and prostatitis.
  • PSA level is generally higher in low-grade tumours than in high-grade tumours. PSA immunohistochemistry is useful in deciding whether the metastasis originated from the prostate or not.
  • The diagnosis of prostatic carcinoma can be made by clinical, biochemical, radiologic, ultrasonographic, cytologic (FNA) and histopathologic methods (core biopsy, TUR specimen, or radical prostatectomy). However, for a definite diagnosis, a triple approach is most commonly followed:

1. 1. 1. DRE or transrectal ultrasound (TRUS),
      2. serum PSA determination, and
      3. TRUS-guided core needle biopsy.

Histologic Grading And Clinical Staging Clinical staging has a good correlation with histologic grading and, thus, has a prognostic significance. Gleason’s histologic grading Gleason’s microscopic grading system is based on two features:

1. Degree of glandular differentiation and distribution.
2. The growth pattern of the tumour in relation to the stroma.

• Based on the above, the microscopic features are assessed by low-power examination of the prostatic tissue and two types of scores (primary for the predominant grade and secondary for the other pattern) are assigned.
• The sum of both primary and secondary scores is expressed as a grade out of 10.
• A new set of the grouping of grades (1-5) based on Gleason score (6-10) has been proposed by the WHO: grade-group 1 with Gleason score ≥6, to grade group 5 with a Gleason score of 9-10.
• TNM staging For clinical staging of prostate cancer, the TNM system is considered an international standard. This system of staging for prostate cancer takes into account cases with abnormal PSA and findings of DRE.
• Based on these parameters, the clinical stages of prostate cancer are given in. Treatment of prostatic carcinoma consists of surgery, radiotherapy and hormonal therapy.
• The hormonal dependence of prostate cancer consists of depriving the tumour cells of the growth-promoting influence of testosterone.
• This can be achieved by bilateral orchiectomy followed by administration of oestrogen. Surgical approaches for prostate cancer include transurethral resection (TUR), radical prostatectomy and transurethral US-guided laser-induced prostatectomy (TULIP).

Diseases of Prostate

• The prostate is divided into the inner periurethral female part (sensitive to oestrogen and androgen) and the outer subcapsular true male part (sensitive to androgen).
• Inflammation of the prostate or prostatitis may be acute, chronic and granulomatous types.
• Nodular hyperplasia of the prostate is common and involves hyperplasia of glandular, fibrous and muscular tissues in varying proportions.
• Cancer of the prostate is the second most common form of cancer in males in the older age group.
• Androgens are considered essential for the development and maintenance of prostatic epithelium.
• Prostatic adenocarcinoma is the most common type of prostatic cancer. It may spread directly to adjacent tissues or may metastasise, especially to bones.
• Diagnosis of prostatic cancer requires DRE, PSA determination and histopathologic examination of core needle biopsy.
• Gleason’s histologic grading and TNM clinical staging are followed for assessing the clinical course of prostate cancer.