Blood Transfusion.pdf

PROSTATE Always remember… The normal prostate consists of: 1. glandular elements 2. stromal elements surrounding the urethra. In the normal adult the prostate weighs approximately 20 gm The prostatic parenchyma can be divided into several biologically distinct regions which are : the peripheral, cen...

PROSTATE Always remember… The normal prostate consists of: 1. glandular elements 2. stromal elements surrounding the urethra. In the normal adult the prostate weighs approximately 20 gm The prostatic parenchyma can be divided into several biologically distinct regions which are : the peripheral, central, transitional, and periurethral zones most hyperplastic lesions arise in the inner transitional and central zones of the prostate, while most carcinomas (70% to 80%) arise in the peripheral zones Adult prostate. central zone (CZ), a peripheral zone (PZ), a transitional zone (TZ), and a periurethral zone. Most carcinomas arise from the peripheral glands of the organ and are often palpable during digital examination of the rectum. Nodular hyperplasia, in contrast, arises from more centrally situated glands and is more likely to produce urinary obstruction early in its course than is carcinoma. The normal histologic appearance of prostate glands and surrounding fibromuscular stroma A small pink concretion (corpora amylacea )seen in benign prostatic glands) appears in the gland just to the left of center. Note the well-differentiated glands with tall columnar epithelial lining cells. These cells do not have prominent nucleoli. categories of prostatic pathology 1. prostatitis 2. nodular hyperplasia, 3. carcinoma. prostatitis Prostatitis may be acute or chronic. Acute bacterial prostatitis: is caused by: the same organisms associated with other acute urinary tract infections, particularly Escherichia coli and other gram-negative rods. Most patients have concomitant infection of the urethra and urinary bladder (acute urethrocystitis). organisms may reach the prostate by : direct extension from the urethra or urinary bladder or by vascular channels from more distant sites. Chronic prostatitis : may follow clinical episodes of acute prostatitis, or may develop insidiously, without previous episodes of acute infection. 2 types: chronic bacterial prostatitis: In some cases bacteria similar to those responsible for acute bacterial prostatitis chronic abacterial prostatitis : Most of cases increased number of leukocytes in prostatic secretions attests to prostatic inflammation, but bacteriologic findings are negative. Sometimes is caused by C. trachomatis and U.urealyticum This is chronic prostatitis. Numerous small dark blue lymphocytes are seen in the stroma between the glands Clinical Features dysuria, urinary frequency, lower back pain, poorly localized suprapubic or pelvic pain. in acute prostatitis :The prostate may be enlarged and tender, fever leukocytosis. Chronic prostatitis, even if asymptomatic, may serve as a reservoir for organisms capable of causing urinary tract infections. Chronic bacterial prostatitis, therefore, is one of the most important causes of recurrent urinary tract infection in men Nodular Hyperplasia Of The Prostate Or Benign Prostatic Hyperplasia BPH extremely common. Start in men by the age of 40, its frequency rises progressively with age, reaching 90% by the eighth decade. Prostatic hyperplasia is characterized by: proliferation of both: stromal and epithelial elements, with resultant: enlargement of the gland and, in some cases, urinary obstruction. Incidence. 20% of men 40 years of age, 70% by age 60 and 90% by age 80. Only 50% of those who have microscopic evidence of BPH have clinically detectable enlargement of the prostate, and of these individuals, only 50% develop clinical symptoms. Etiology incompletely understood, Despite the fact that there is an increased number of epithelial cells and stromal components in the periurethral area of the prostate, there is no clear evidence of increased epithelial cell proliferation in human BPH. Instead, it is believed that the main component of the “hyperplastic” process is impaired cell death. 90% of total prostatic androgens, is dihydrotestosterone (DHT). It is formed in the prostate from the conversion of testosterone by the enzyme type 2 5αreductase. This enzyme is located almost entirely in stromal cells; DHT binds to the nuclear androgen receptor (AR) present in both stromal and epithelial prostate cells. Binding of DHT to AR activates the transcription of androgen-dependent genes. results in the increased production of several growth factors and their receptors. Most important among these are members of the fibroblast growth factor (FGF) family, and particularly FGF-7 FGF-7, produced by stromal cells, is probably the most important factor mediating the paracrine regulation of androgen-stimulated prostatic growth. Other growth factors produced in BPH are FGFs 1 and 2, and TGFβ, which promote fibroblast proliferation. Although the ultimate cause of BPH is unknown, it is believed that DHT-induced growth factors act by increasing the proliferation of stromal cells and decreasing the death of epithelial cells. Morphology Grossly … arises most commonly in the inner, periurethral glands of the prostate, the affected prostate is enlarged, prostate weighs between 60 and 100 gm The cut surface contains many fairly well-circumscribed nodules that bulge from the cut surface The urethra is usually compressed by the hyperplastic nodules, often to a slitlike orifice. Nodular prostatic hyperplasia. Well-defined nodules compress the urethra (arrowheads) into a slitlike lumen benign prostatic hyperplasia. Nodules appear mainly in the lateral lobes Microscopically… the hyperplastic nodules are composed of : proliferating glandular elements and fibromuscular stroma. The hyperplastic glands are lined by tall, columnar epithelial cells and a peripheral layer of flattened basal cells; The glandular lumina often contain inspissated, proteinaceous secretory material, termed corpora amylacea. Nodular hyperplasia. Awell-demarcated nodule at the top of the field, populated by hyperplastic glands B, Higher power photomicrograph demonstrates the morphology of the hyperplastic glands, with the characteristic dual cell population: the inner columnar secretory cells, and the outer flattened basal cell layer. Microscopically, benign prostatic hyperplasia can involve both glands and stroma, though the former is usually more prominent. Here, a large hyperplastic nodule of glands is seen. Clinical Features 1. 2. occur in only about 10% of men with the disease. most common :urinary tract obstruction. These include : difficulty in starting the stream of urine (hesitancy) and intermittent interruption of the urinary stream while voiding. 3. Some men may develop complete urinary obstruction, with resultant painful distention of the bladder and, if neglected, hydronephrosis 4. urinary urgency, frequency, and nocturia, all indicative of bladder irritation. 5. The combination of residual urine in the bladder and chronic obstruction increases the risk of urinary tract infections. The enlarged prostate gland seen here not only has enlarged lateral lobes, but also a greatly enlarged median lobe that obstructs the prostatic urethra. This led to obstruction with bladder hypertrophy, as evidenced by the prominent trabeculation of the bladder wall seen here from the mucosal surface. Obstruction with stasis also led to the formation of the yellow-brown calculus (stone). Obstruction from nodular prostatic hyperplasia has led to prominent trabeculation seen on the mucosal surface of this bladder with hypertrophy. Treatment α-blockers, which decrease prostate smooth muscle tone via inhibition of α1-adrenergic receptors Inhibitors of 5-α-reductase Transurethral resection of the prostate (TURP) A frequently performed operation for symptomatic nodular prostatic hyperplasia is a transurethral resection, which yields the small "chips" of rubbery prostatic tissue seen here. noteeeeeeeeeeeeeeee Nodular hyperplasia is not considered to be a premalignant Carcinoma of the Prostate the most common visceral cancer in males, second most common cause of cancer-related deaths in men, after carcinoma of the lung. predominantly a disease of older males, peak incidence between ages of 65 and 75 years. Latent cancers of the prostate are more common than those that are clinically apparent, overall frequency of more than 50% in men older than 80 years of age. Etiology the cause is unknown, clinical and experimental observations suggest: 1. hormones, 2. genes, and 3. environment all have a role in its pathogenesis. clinical and experimental observations: hormones??? It does not develop in males castrated before puberty, indicating that androgens probably contribute to its development. the observation that the growth of many carcinomas of the prostate can be inhibited by orchiectomy or by the administration of estrogens clinical and experimental observations: genes??? increased risk of disease among first-degree relatives of patients with prostate cancer. Symptomatic carcinoma of the prostate is more common and occurs at an earlier age in blacks than in whites, Much effort is focused on finding prostate cancer genes, but no definitive data are available. clinical and experimental observations: environment ??? A possible role for environmental influences is suggested by: 1. the increased frequency of prostatic carcinoma in certain industrial settings and 2. by significant geographic differences in the incidence of the disease. Carcinoma of the prostate is particularly common in Scandinavian countries and relatively uncommon in Japan and certain other Asian countries. Morphology 70-80% of prostate cancers arise in the outer (peripheral) glands and hence may be palpable as irregular hard nodules by rectal digital examination. Because of the peripheral location, prostate cancer is less likely to cause urethral obstruction in its initial stages than is nodular hyperplasia. Early lesions typically appear as ill-defined masses just beneath the capsule of the prostate. Metastases to regional pelvic lymph nodes may occur early. Locally advanced cancers often infiltrate the seminal vesicles and periurethral zones of the prostate and may invade the adjacent soft tissues and the wall of the urinary bladder. Invasion of the rectum therefore is less common than is invasion of other contiguous structures. Adenocarcinoma of the prostate. Carcinomatous tissue is seen on the posterior aspect (lower left). Note the solid whiter tissue of cancer in contrast to the spongy appearance of the benign peripheral zone on the contralateral side. These sections through a prostate removed via radical prostatectomy reveal irregular yellowish nodules, mostly in the posterior portion (seen here superiorly). This proved to be prostatic adenocarcinoma. Microscopically, most prostatic carcinomas are adenocarcinomas composed of small glands that infiltrate the adjacent stroma the glands in carcinomas lie "back to back" The neoplastic glands are lined by a single layer of cuboidal cells Always remember… Prostate adenocarcinoma are not necessarily enlarged. Adenocarcinoma may also coexist with hyperplasia A. Adenocarcinoma of the prostate demonstrating small glands crowded in between larger benign glands. B, Higher magnification shows several small malignant glands with enlarged nuclei, prominent nucleoli, and dark cytoplasm, as compared with the larger benign gland At the right are normal prostatic glands containing scattered corpora amylacea. At the left is prostatic adenocarcinoma. Note how the glands of the carcinoma are small and crowded. At high magnification, the neoplastic glands of prostatic adenocarcinoma are still recognizable as glands, but there is no intervening stroma and the nuclei are hyperchromatic Prominent nucleoli are seen in the nuclei of this prostatic adenocarcinoma, which is a characteristic feature. prostatic intraepithelial neoplasia Glands adjacent to areas of invasive carcinoma of the prostate often contain foci of epithelial atypia, or prostatic intraepithelial neoplasia (PIN). Because of its frequent coexistence with infiltrating carcinoma, PIN has been suggested as a probable precursor to carcinoma of the prostate. This is prostatic intraepithelial neoplasia (PIN), a precancerous cellular proliferation found in a single acinus or small group of acini. PIN can be low or high grade (as seen here). The finding of PIN suggests that prostatic adenocarcinoma may also be present Clinical Features often clinically silent, particularly during their early stages. 10% of localized carcinomas are discovered unexpectedly, during histologic examination of prostate tissue removed for nodular hyperplasia. Because most cancers begin in the peripheral regions of the prostate, they may be discovered during routine digital rectal examination. More extensive disease may produce signs and symptoms of "prostatism," including : local discomfort and evidence of lower urinary tract obstruction similar to that encountered in patients with nodular hyperplasia. Physical examination reveals a hard, fixed prostate. More aggressive carcinomas of the prostate may first come to clinical attention because of the presence of metastases. Bone metastases, particularly to the axial skeleton, are common and may cause either osteolytic (destructive) or, more commonly, osteoblastic (bone-producing) lesions. The presence of osteoblastic metastases in an older male is strongly suggestive of advanced prostatic carcinoma Diagnosis serum levels of prostate-specific antigen (PSA) PSA is produced by both normal and neoplastic prostatic epithelium. PSA is secreted in high concentrations into prostatic acini and thence into seminal fluid, where it increases sperm motility by maintaining seminal secretions in a liquid state. serum PSA level of 4.0 ng/L has been used as the upper limit of normal. Causes of elevated PSA 1.adenocarcinoma, 2.nodular hyperplasia, and 3.prostatitis, in a minority of cases of cancer of the prostate,, serum PSA is not elevated. Its diagnostic value is enhanced considerably, when it is used in conjunction with other procedures, such as : 1. digital rectal examination, 2. Transrectal sonography, 3. needle biopsy serum PSA is of great value in monitoring patients after treatment for prostate cancer, with rising levels after ablative therapy indicative of recurrence and/or the development of metastases. Treatment combinations of: surgery, radiation therapy, and hormonal manipulations. Hormonal therapy has a central role in the treatment of advanced carcinomas. Specifically, most prostate cancers are androgen sensitive and are inhibited to some degree by androgen ablation. Surgical or pharmacologic castration, estrogens, and androgen receptor-blocking agents