Ureter pathology and urinary bladder.pptx

The main pathological lesions involving the ureter include:
Congenital Anomalies:
* Double and bifid ureters
* Ureteropelvic junction (UPJ) obstruction

Obstructive Lesions: as a result of calculi, tumours, blood clots

Primary malignant tumours:
Primary malignant tumours of the ureter follow patterns similar to those arising in the renal pelvis, calyces, and bladder, and a majority are urothelial carcinomas.
Primary tumors of the ureter are rare.
Cystitis takes many forms.
Most cases stem from nonspecific acute or chronic inflammation of the bladder.
Etiology:
The common etiologic agents of bacterial cystitis are coliform bacteria.
Patients receiving cytotoxic antitumor drugs, such as cyclophosphamide, sometimes develop hemorrhagic cystitis.
Adenovirus infection also causes a hemorrhagic cystitis.
Several distinct variants of cystitis are defined by either morphologic appearance or causation (Interstitial cystitis, Malakoplakia, Polypoid cystitis).
Various metaplastic lesions may occur in the bladder:

Cystitis glandularis: Nests of urothelium (Brunn nests) may grow downward into the lamina propria, and their central epithelial cells may variously differentiate into a cuboidal or columnar epithelium lining.
Cystitis cystica: cystic spaces filled with clear fluid lined by flattened urothelium.
intestinal or colonic: goblet cells resembling intestinal mucosa (metaplasia).

As a response to injury, the urothelium often undergoes squamous metaplasia, which must be differentiated from normal glycogenated squamous epithelium, commonly found at the trigone in women.
Bladder cancer accounts for approximately 7% of cancers and 3% of cancer deaths in the United States.
The vast majority of bladder cancers (90%) are urothelial carcinomas.
more common in men than in women.
About 80% of patients are between the ages of 50 and 80 years.
Bladder cancer, with rare exceptions, is not familial.
Some of the most common factors implicated in the causation of urothelial carcinoma include:
cigarette smoking
various occupational carcinogens
Schistosoma haematobium infections in areas where it is endemic, such as Egypt.

1. Pathology of URETER, BLADDER, AND URETHRA

2. URETER & BLADDER Congenital Anomalies. Non-neoplastic conditions. Neoplastic conditions.

3. The renal pelvis, ureters, bladder, and urethra (except the terminal portion) are lined by " Urothelium " . Beneath the mucosa are the lamina propria and, deeper yet, the muscularis propria (detrusor muscle), which makes up the bladder wall.

4. Ureter The main pathological lesions involving the ureter include : Congenital Anomalies: * Double and bifid ureters * Ureteropelvic junction (UPJ) obstruction Obstructive Lesions: as a result of calculi, tumours, blood clots Primary malignant tumours: Primary malignant tumours of the ureter follow patterns similar to those arising in the renal pelvis, calyces, and bladder, and a majority are urothelial carcinomas. Primary tumors of the ureter are rare.

5. Double and bifid ureters Double ureters are almost invariably associated with totally distinct double renal pelves or with the anomalous development of a large kidney having a partially bifid pelvis terminating in separate ureters. Double ureters may pursue separate courses to the bladder but commonly are joined within the bladder wall and drain through a single ureteral orifice. Most are unilateral and of no clinical significance.

6. Ureteropelvic junction (UPJ) obstruction Congenital disorder, results in hydronephrosis. It usually manifests in infancy or childhood, much more commonly in boys. It is the most frequent cause of hydronephrosis in infants and children. Grossly: the renal pelvis is markedly dilated, but the ureter is not, indicating that the point of obstruction is at the ureteropelvic junction

7. Ureteropelvic junction (UPJ) obstruction

8. Retroperitoneal fibrosis It is an uncommon cause of ureteral narrowing or obstruction characterized by a fibrous proliferative inflammatory process encasing the retroperitoneal structures and causing hydronephrosis. The disorder occurs in middle to old age. The affected sites include: the pancreas, retroperitoneum, and salivary glands, to mention a few.

9. Retroperitoneal fibrosis

10. bladder or vesical diverticulum Consists of a pouchlike Evagination of the bladder wall. Diverticula may be congenital but more commonly are acquired lesions that arise as a consequence of persistent urethral obstruction. Although most diverticula are small and asymptomatic, they sometimes lead to urinary stasis and predispose to infection.

11. Cystitis Cystitis takes many forms. Most cases stem from nonspecific acute or chronic inflammation of the bladder. Etiology : The common etiologic agents of bacterial cystitis are coliform bacteria. Patients receiving cytotoxic antitumor drugs, such as cyclophosphamide, sometimes develop hemorrhagic cystitis. Adenovirus infection also causes a hemorrhagic cystitis. Several distinct variants of cystitis are defined by either morphologic appearance or causation (Interstitial cystitis, Malakoplakia, Polypoid cystitis).

12. Interstitial cystitis (chronic pelvic pain syndrome) is a persistent, painful form of chronic cystitis occurring most frequently in women. It is characterized by intermittent, often severe suprapubic pain, urinary frequency, urgency, hematuria and dysuria without evidence of bacterial infection. There are cystoscopic findings of fissures and punctate hemorrhages (glomerulations) in the bladder mucosa. The histologic findings are nonspecific . Late in the course, transmural fibrosis may ensue, leading to a contracted bladder .

13. No epithelium and plenty of ulceration. Not high powered, therefore can't see mast cells. Difficult to treat due to unknown etiology.

14. Malakoplakia Malakoplakia: from Greek Malako "soft" + Plako "plaque" Most commonly occurs in the bladder. Results from defects in phagocytic or degradative function of macrophages , such that phagosomes become overloaded with undigested bacterial products. The macrophages have abundant granular cytoplasm filled with phagosomes stuffed with particulate and membranous bacterial debris. In addition, laminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes, known as Michaelis-Gutmann bodies , typically are present within the macrophages.

15. Polypoid cystitis Is an inflammatory condition resulting from irritation to the bladder mucosa in which the urothelium is thrown into broad bulbous polypoid projections as a result of marked submucosal edema . Polypoid cystitis may be confused with papillary urothelial carcinoma both clinically and histologically.

16. Metaplasia Various metaplastic lesions may occur in the bladder: Cystitis glandularis : Nests of urothelium ( Brunn nests) may grow downward into the lamina propria, and their central epithelial cells may variously differentiate into a cuboidal or columnar epithelium lining. Cystitis cystica : cystic spaces filled with clear fluid lined by flattened urothelium. intestinal or colonic : goblet cells resembling intestinal mucosa (metaplasia). As a response to injury, the urothelium often undergoes squamous metaplasia, which must be differentiated from normal glycogenated squamous epithelium, commonly found at the trigone in women.

17. Metaplasia ( Brunn nests) Solid nests of benign urothelial cells often with regular contour. Cells have normal cytology and orderly arrangement.

18. Metaplasia (Cystitis glandularis ) similar to cystitis cystica but with luminal cuboidal or columnar cells surrounded by urothelial cells

19. Metaplasia (Cystitis cystica ) May appear grossly as pearly or luminescent cysts with intact surface urothelium . Well-defined nests of urothelium with a centrally dilated lumen (like von Brunn's nests but with a hole in the middle).

20. Intestinal metaplasia identical to typical cystitis glandularis but with presence of goblet cells

21. Metaplasia Both cystitis cystica and glandularis

22. Neoplasms Bladder cancer accounts for approximately 7% of cancers and 3% of cancer deaths in the United States. The vast majority of bladder cancers ( 90% ) are urothelial carcinomas. more common in men than in women. About 80% of patients are between the ages of 50 and 80 years. Bladder cancer, with rare exceptions, is not familial. Some of the most common factors implicated in the causation of urothelial carcinoma include: cigarette smoking various occupational carcinogens Schistosoma haematobium infections in areas where it is endemic, such as Egypt.

23. PATHOGENESIS of Bladder cancers Genetic Models for bladder carcinogenesis include: First pathway : tumor is initiated by deletions of tumor-suppressor genes on 9p and 9q, leading to formation of superficial papillary tumors, a few of which may then acquire TP53 mutations and progress to invasion. second pathway , possibly initiated by TP53 mutations, leads first to carcinoma in situ and then, with loss of chromosome 9, progresses to invasion. The underlying genetic alterations in superficial tumors include fibroblast growth factor receptor 3 (FGFR3) mutations and activation of the Ras pathway.

24. MORPHOLOGY Two distinct precursor lesions to invasive urothelial carcinoma are recognized: Noninvasive papillary neoplasms (maybe low or high grade) Flat noninvasive carcinoma in situ (uniformly high grade). In about half of the patients with invasive bladder cancer, no precursor lesion is found; in such cases, it is presumed that the precursor lesion was overgrown by the high-grade invasive component.

25. Non invasive papillary urothelial neoplasms The most common precursor lesion to invasive urothelial carcinoma. Demonstrate range of atypia and are graded to reflect their biologic behavior The most common grading system classifies tumors as follows: Papilloma. Papillary urothelial neoplasm of low malignant potential (PUNLMP). Low grade papillary urothelial carcinoma. High grade papillary urothelial carcinoma

26. Non invasive papillary urothelial neoplasms

27. Carcinoma in situ (cis) CIS is defined by the presence of cytologically malignant cells within a flat urothelium. CIS commonly is multifocal and sometimes involves most of the bladder surface or extends into the ureters and urethra. On cystoscopic examination it may appear only as a flat area of erythema or granularity. It is often multifocal CIS is often asymptomatic . Without treatment, 50% to 75% of CIS cases progress to muscle-invasive cancer

28. The atypical cells form a disorganized epithelial layer that occupies the full thickness of the urothelium but does not invade through the basement membrane . Carcinoma in situ (cis)

29. Invasive urothelial cancer Invasive urothelial cancer associated with papillary urothelial cancer (usually of high grade) or CIS may superficially invade the lamina propria or extend more deeply into underlying muscle. Underestimation of the extent of invasion in biopsy specimens is a significant problem. The extent of invasion and spread (staging) at the time of initial diagnosis is the most important prognostic factor. Almost all infiltrating urothelial carcinomas are of high grade.

30. Other Epithelial Bladder Tumors SQUAMOUS CELL CARCINOMAS: RESEMBLING SQUAMOUS CANCERS OCCURRING AT OTHER SITES MAKE UP ABOUT 3% TO 7% OF BLADDER CANCERS IN THE UNITED STATES BUT ARE MUCH MORE COMMON IN COUNTRIES WHERE URINARY SCHISTOSOMIASIS IS ENDEMIC. PURE SQUAMOUS CELL CARCINOMAS ARE NEARLY ALWAYS ASSOCIATED WITH CHRONIC BLADDER IRRITATION AND INFECTION. MIXED UROTHELIAL CARCINOMAS WITH AREAS OF SQUAMOUS CARCINOMA ARE MORE FREQUENT THAN PURE SQUAMOUS CELL CARCINOMAS. MOST ARE INVASIVE, FUNGATING TUMORS OR ARE INFILTRATIVE AND ULCERATIVE. THE LEVEL OF CELLULAR DIFFERENTIATION VARIES WIDELY, FROM WELL DIFFERENTIATED LESIONS PRODUCING ABUNDANT KERATIN TO ANAPLASTIC TUMORS WITH ONLY FOCAL EVIDENCE OF SQUAMOUS DIFFERENTIATION.

31. Squamous cell carcinoma Gross: large necrotic mass that is typically invasive Keratin production

32. Other Epithelial Bladder Tumors Adenocarcinomas of the bladder are rare and are histologically identical to adenocarcinomas seen in the gastrointestinal tract. Some arise from urachal remnants in the dome of the bladder or in association with extensive intestinal metaplasia.

33. Staging of bladder cancers Grading : tumor grade is the description of a tumor based on how abnormal the tumor cells and the tumor tissue look under a microscope. Staging: cancer stage refers to the size and/or extent (reach) of the original (primary) tumor and whether or not cancer cells have spread in the body. According to the TNM staging system (Tumor, Lymph node, Metastasis),The majority of bladder cancers fall into one of the following categories:

34. Staging of bladder cancers (TNM)

35. Clinical features Bladder tumors most commonly present with painless hematuria . The risk of recurrence is related to several factors , including tumor size, stage, grade, multifocality, mitotic index, and associated dysplasia and/or CIS in the surrounding mucosa. Most recurrent tumors arise at sites different than that of the original lesion, yet share the same clonal abnormalities as those of the initial tumor, thus, these are true recurrences that stem from shedding and implantation of the original tumor cells at new sites. high-grade papillary urothelial carcinomas frequently are associated with either concurrent or subsequent invasive urothelial carcinoma. lower-grade papillary urothelial neoplasms often recur but infrequently invade

36. treatment The treatment for bladder cancer depends on tumor grade and stage and on whether the lesion is flat or papillary. For small localized papillary tumors that are not high grade: transurethral resection . Patients with tumors that are at high risk for recurrence or progression typically receive topical immunotherapy consisting of intravesical instillation of an attenuated strain of the tuberculosis bacillus called Bacille Calmette-Guérin (BCG). Patients are closely monitored for tumor recurrence with periodic cystoscopy and urine cytologic studies for the rest of their lives. Radical cystectomy typically is reserved for (1) tumor invading the muscularis propria; (2) CIS or high-grade papillary cancer refractory to BCG; and ( 3) CIS extending into the prostatic urethra and down the prostatic ducts, where BCG cannot contact the neoplastic cells. Advanced bladder cancer is treated using chemotherapy , which can palliate but is not curative.

37. Tumors of the urethra Primary carcinoma of the urethra is an uncommon lesion Tumors arising within the proximal urethra tend to show urothelial differentiation and are analogous to those occurring within the bladder. lesions found within the distal urethra are more often squamous cell carcinomas. Adenocarcinomas are infrequent in the urethra and generally occur in women. Cancers arising within the prostatic urethra are dealt with in the section on the prostate.

38. References Robbins basic pathology. Robbins and Cotran atlas of pathology. Husain A. Sattar. Fundamentals of pathology. Robbins and Cotran pathologic basis of disease. Harsh Mohan. Textbook of PATHOLOGY.