Pathology Notes

Practice question answers Lower urinary tract pathology © Jun Wang, MD, PhD 1. C. Hematuria may be caused by various disorders. Outpouching of ureter without atypical cells are most consistent with diverticula . Urothelial carcinoma of ureter usually presents with mass (filling defects, obstruction, etc) during image studies. In addition, all urothelial neoplasms likely have atypical cells identified in urine, same as bladder cancers . 2. E. The patients presents with symptoms of bilateral urinary obstruction. Image studies reveal a pelvic mass. Microscopic finding of fibrous tissue without atypia is most compatible with a benign fibrotic process, i.e. sclerosing retroperitoneal fibrosis , a condition of IgG4 associated diseases. The plasma cells usually contains IgG4. Diffuse large B cell lymphoma is characterized by sheets of markedly atypical cells expressing CD20, not scattered lymphocytes and plasma cells. Fibrosarcoma is characterized by hypercellular spindle cel

Practice questions Lower urinary tract pathology © Jun Wang, MD, PhD 1. A 45-year-old man presents with intermittent painless hematuria and dysuria for a month. His past medical history is unremarkable. Physical examinations reveals no significant abnormality. Laboratory tests are normal except 6 red cells per high power field in urinalysis. No white cells, casts or abnormal epithelial cells are seen. Intravenous pyelogram reveal normal filling of renal pelvis and bladder. The ureters are patent with a few outpouchings at the mid and distal segments. What is the most likely diagnosis? A. High grade urothelial carcinoma of ureter B. Low grade urothelial carcinoma of ureter C. Ureter diverticula D. Urothelial carcinoma in situ of ureter 2. Use this case for next two questions . A 40-year-old man presents with vague low back pain for 4 months. He has a history of classic Hodgkin lymphoma of cervical lymph nodes 15 years ago, that was treated with chemotherapy, and Rie

Bladder cancers   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Most common malignancy in urinary system Ninth most common malignancy worldwide More common in older population, white, male Risk factors Chemical carcinogens: aromatic amines, etc Cigarette smoking Arsenic Chronic cystitis Human papilloma virus Iatrogenic: Radiation, cyclophosphamide , analgesics, etc Others: Family history, genetic, etc Classification Urothelial cancers Papillary urothelial neoplasms with low malignant potential Non-invasive papillary urothelial carcinoma Urothelial carcinoma in situ Invasive urothelial carcinoma Squamous cell carcinoma Adenocarcinoma Back to lower urinary tract pathology Back to contents

Urothelial papilloma   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Most common in posterior or lateral walls Usually adult May occur in children Clinical presentations Asymptomatic or hematuria Key morphological features Benign papillary growth Central fibrovascular core Urothelium of normal thickness (less than 7 layers) No cytological atypia Genetics Activating mutation of KRAS or HRAS FGFR3 mutation Treatment Surgery Back to lower urinary tract pathology Back to contents

Urothelial carcinoma in situ   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Commonly multifocal Commonly associated with invasive carcinoma Clinical presentations Hematuria Markedly atypical cells in urine (seen in any high grade urothelial carcinoma of any location along urinary tract) Key morphological features Flat lesion with marked pleomorphism NO invasion Markedly atypical cells Genetics Complex abnormalities, detected by FISH ( Urovysion , etc) Various mutations, including Rb Treatment bCG, hyperthermia, mitomycin-C, surgery Back to lower urinary tract pathology Back to contents

Urethra disorders   Updated: 01/27/2021 © Jun Wang, MD, PhD Urethritis Gonococcal Non-gonococal: may be associated with Reiter syndrome (urethritis, conjunctivitis, arthritis) Associated with prostatitis and cystitis Caruncle Only in female Commonly in postmenopausal women Small protruding from external urethral meatus Reactive polypoid lesion with inflamed granulation features May cause bleeding or infection Treatment: Excision Prognosis: Likely recur Urethral tumors Benign Papilloma Condyloma Malignant Primary carcinoma uncommon Usually urothelial, squamous, or adenocarcinoma More common in women Associated with chronic irritation (chronic catheterization/urethroplasty), urethral strictures, radiation therapy, urethritis secondary to sexually transmitted diseases and recurrent urinary tract infections Secondary involvement by urothelial carcinoma of bladder most common Back to lower urinary tract pathology Back to contents

Ureter disorders Updated: 11/03/23 © Jun Wang, MD, PhD Ureteral obstructions Intrinsic Stones, usually lodge at (a) ureteropelvic junction, (b) where ureters cross iliac artery and (c) where ureters enter bladder Strictures (congenital or due to sclerosing retroperitoneal fibrosis ) Tumors, blood clots, neurogenic causes. Extrinsic Pregnancy, local inflammation, endometriosis, local tumors Sclerosing retroperitoneal fibrosis Adults 40+ Usually idiopathic ; others associated with ergot derivatives, beta blockers, adjacent inflammation, local tumors Associated with mediastinal fibrosis, sclerosing cholangitis, Riedel thyroiditis Associated with the spectrum of IgG4 associated disease Fibrous tissue with infiltrate of IgG4-positive plasma cells, and other inflammatory cells Clinical features: Pain (Lower back, abdomen), obstructive uropathy Diagnosis: Image, biopsy Treatment: Relieve obstruction (stents, etc), stop fibrotic process (glucocorticoids, etc)

Papillary urothelial neoplasms of low malignant potential   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Most common in lateral posterior walls and ureteric orifices More common in male, older population May occur in children Clinical presentations Asymptomatic or hematuria Key morphological features Resembles the exophytic urothelial papilloma Increased cellular proliferation exceeding the thickness of normal urothelium (> 7 layers) Minimal cytological atypia Genetics No specific findings Treatment Surgery Back to lower urinary tract pathology Back to contents

Non-invasive papillary urothelial carcinoma   Updated: 01/26/2021 © Jun Wang, MD, PhD General features More common in male, older population Commonly multifocal Clinical presentations Hematuria Atypical cells in urine Key morphological features Papillary growth Increased cellular proliferation exceeding the thickness of normal urothelium (> 7 layers) Architectural atypia such as fusion of papillae NO invasion Graded by cytological atypia Low grade : slightly disorganized architecture and mild variation in nuclear shape, size, darkness, etc High grade : moderate to marked architectural and cytological pleomorphism (great variation of nuclear shape, size, darkness, brisk mitosis, etc) Genetics Low grade: no specific findings, including FGFR3 High grade: aneuploidy, p53, Her2, EGFR, loss of p21Waf1 or p27kip1 Treatment Low grade: surgery High grade: surgery, chemotherapy, radiation therapy Back to lower urinary tract pathology Back to

Invasive urothelial carcinoma   Updated: 01/27/2021 © Jun Wang, MD, PhD General features Most common bladder tumor More common in >50, cigarette smoker, men, urban Multifocal along urinary tract Risk factors Cigarette smoking Industrial exposure to arylamines and aniline dyes Long term phenacetin use in young women Cyclophosphamide Chronic irritation HPV Clinical presentations Painless hematuria Obstruction if near ureteral orifices Irritative bladder symptoms: Dysuria, urgency, etc Atypical cells in urine Key morphological features Mass, with or without ulceration Nest, cord of atypical urothelial cells, low or high grade Invasion into stroma Positive for uroplakin , etc Genetics Aneuploidy Monosomy 9, 9p-, etc Low grade papillary: FGFR3, PIK3CA, STAG2 High grade: p53, RB1, Her2, PTEN, etc Treatment Surgery: cystectomy Chemotherapy Back to lower urinary tract pathology Back to contents

Squamous cell carcinoma of bladder   Updated: 01/27/2021 © Jun Wang, MD, PhD General features <5% of bladder tumors in US More common in Egypt/Sudan Diagnosed only if solely squamous cell component Commonly lateral walls and trigone Arises from squamous metaplasia Risk factors Cigarette smoking Chronic infection Bladder exstrophy, neurogenic bladder, chronic indwelling catheters Schistosoma haematobium infection in Egypt/Sudan Clinical presentations Painless hematuria Irritative voiding syndrome Key morphological features Cords, nests of atypical cells with squamous differentiation ( intercellular bridge, squamous pearl ,etc) Invading stroma Genetics Complex, nonspecific Treatment Surgery Preoperative radiation therapy may be considered Back to lower urinary tract pathology Back to contents

Malakoplakia of bladder   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Rare histiocytic diseas Common in GU tract, particularly bladder  May occur in other locations More common in immunocompromised, women Key pathogenesis Defects in histiocytic phagocytic or degradative functions of bacteria Intracellular deposition of iron and calcium may occur Clinical presentations Urinary symptoms and urinary tract infection Key morphological features Soft raised plaque Foamy histiocytes with PAS+ granular eosinophilic cytoplasm in lamina propria Histiocytes with increased number of phagosomes containing non-digested bacteria, Michaelis-Gutmann bodies (iron containing, cytoplasmic laminated mineralized concretions) Treatment Antibiotics that concentrate in macrophages Back to lower urinary tract pathology Back to contents

GU tract congenital anomalies   Updated: 01/27/2021 © Jun Wang, MD, PhD Ureter anomalies Double and bifid ureters: Associated with duplication of renal pelvis Ureteropelvic junction (UPJ) obstruction Most common causes of hydronephrosis in children May be associated with agenesis of contralateral kidney Diverticula Asymptomatic or associated with recurrent urinary tract infections Outpouching identified by image studies (Intravenous pyelogram, etc) Bladder anomalies Vesicoureteral reflux : Risk for infection and reflux nephropathy Diverticula : Predominantly in men; risk for infection and stone Exstrophy of the bladder Bladder mucosa exposed to the surface exterior Defect in the anterior abdominal wall Developmental failure Risk for adenocarcinoma of bladder Patent urachus Failure of urachal canal obliteration Urination through umbilicus Risk for infection and adenocarcinoma May be associated with urachal cysts Penile anomalies Hypospadias Most

Adenocarcinoma of bladder   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Malignant tumor with glandular differentiation Diagnosed if pure adenocarcinomas More common in men, mean age 68 Usually lateral wall or trigone Risk factors Intestinal metaplasia Chronic irritation of bladder Clinical presentations Painless hematuria Irritative voiding syndrome Key morphological features Irregular glands lined by atypical cells invading stroma Genetics Complex Treatment Surgery Back to lower urinary tract pathology Back to contents

Cystitis and metaplasia   Updated: 02/01/2022 © Jun Wang, MD, PhD General features Inflammation of bladder Urinary symptoms: Dysuria, urinary urgency and frequency, hematuria, etc More common in women, except polypoid cystitis Acute cystitis Clinical diagnosis More common in women of reproductive age Usually bacterial infection, most common E. coli, proteus, etc May spread to kidney, causing pyelonephritis Pyuria, positive microbiology studies Treatment: antibiotics Chronic cystitis Chronic bladder inflammation Refractory to treatment or surgical correction Recurrence common Interstitial cystitis Definition Unpleasant sensation: pain, pressure, etc Related to urinary bladder Urinary tract symptoms > 6 months duration No evidence of infection or other irritations Unclear etiology Cystoscopic findings Mucosal fissures Petechia Pathological findings May have normal histology Increased mast cell infiltration Other chronic inflammatory cell infiltration