CARCINOMA UROTELIAL DE VÍAS URINARIAS

Dr. A López-Beltrán

Córdoba

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CARCINOMA UROTELIAL DE VÍAS URINARIAS

Tumor-like Lesions of the Urinary

Bladder

A Lopez-Beltran

Cordoba

Tumor-like Lesions of the Urinary Bladder

• Malakoplakia• Polyps• - Fibroepithelial– - Other

• Amyloidosis• Endometriosis• Endocervicosis• Mullerianosis• Postoperative spindle cell nodule

• Inflammatory pseudotumor• Paraganglionic tissue

• Epithelial abnormalities:

• - Von Brunn’s nests

• - Cystitis glandularis

• - Cystitis cystica

• - Squamous metaplasia

• - Nephrogenic adenoma

• - Papillary hyperplasia

• Non-specific cystitis:

• - Papillary-polypoid cystitis

• Specific cystitis:

• - Radiation cystitis

Cystitis Glandularis, usual type

Cystitis Glandularis, intestinal type

Pools of extravasated mucin associated with minimal stromal reaction Mucin in stroma associated with intestinal-type glands

Cystitis Glandularis with Mucin Extravasation:

• Orderly distribution

• No cells floating in mucin

• Lack of atypia of lining cells

• No muscularis propria invasion

Florid Cystitis Glandularis of Intestinal Florid Cystitis Glandularis of Intestinal Type with Mucin ExtravasationType with Mucin Extravasation

Differential Diagnosis

Endocervicosis

Bladder Adenocarcinoma

Urachal Adenocarcinoma

Metastatic Rectal Adenocarcinoma

BLADDER ADENOCARCINOMABLADDER ADENOCARCINOMA

URACHAL ADENOCARCINOMA: Rare mucinous extravasation

CK20 positive with variable CK7 positivity/B-Catenin nuclear

COLLOID CARCINOMA FROM RECTUM

COLLOID CARCINOMA FROM RECTUM

Bladder Adenocarcinoma

• Immunohistochemical profile intermediate between urothelial and colorectal carcinoma . Nuclear B-Catenin

•More frequently CK7 and thrombomodulin while colon carcinoma expresses more frequently CK20 and β-catenin nuclear-cytoplasmic

• CDX2 and villin positivity favor colorectal carcinoma

83% vs. 0%

80% vs. 4%

17% vs. 100%

-/-

•Different immunoprofile

•Different pathway to intestinal

metaplasia as compared

to other organs

NEPHROGENIC ADENOMANEPHROGENIC ADENOMA4-81 Yrs (Av 41 yrs)

M:F = 2:1GU Surgery: 61%GU Stones: 14%GU Trauma: 9%

Renal Transplant: 8%

Bladder 80%Urethra 12% (1/4 TIC)Ureter 8%

Location:

NEPHROGENIC ADENOMANEPHROGENIC ADENOMA

Papillary 56%Polypoid 10%Sessile 34%

At least 17% multiple

Atypical Nephrogenic AdenomaAtypical Nephrogenic AdenomaCheng, Cheville, Sebo, Eble and Bostwick

Cancer 2000;88:853-61

• Nuclear enlargement

• Enlarged nucleoli

NO MITOTIC

ACTIVITY

but

WORRISOME FEATURES:

HOBNAILING CELLS

CELLS WITH CLEAR CYTOPLASM

SIGNET RING-LIKE CELLS

Fibromyxoid Nephrogenic Adenoma: Fibromyxoid Nephrogenic Adenoma: A Newly Variant Mimicking Mucinous A Newly Variant Mimicking Mucinous AdenocaAdenoca

Hansel D, Am J Hansel D, Am J SurgSurg PatholPathol 2007;318:12312007;318:1231--12371237

NEPHROGENIC ADENOMANEPHROGENIC ADENOMADifferential Diagnosis

• Clear cell carcinoma• Nested variant of transitional cell carcinoma• Prostatic carcinoma (urethra)• Signet ring cell carcinoma, primary or metastatic

CLEAR CELL CARCINOMACLEAR CELL CARCINOMA

Deceptive low-power appearance !

Nephrogenic AdenomaNephrogenic Adenoma Clear Cell CarcinomaClear Cell Carcinoma

Male predominance Female predominanceHistory of trauma No past historyUsually small Commonly large massesHobnail cells uncommon Hobnail cells frequentClear cells infrequent Clear cells commonMild cytologic atypia Moderate to severe

cytologic atypiaMitotic activity < 1/10 Brisk mitotic activityNo association with TCC +/- TCCor endometriosis +/- endometriosisLow MIB-1 expression High MIB-1 expressionp53 (-) p53 (+)

IMMUNOHISTOCHEMICAL PROFILESIMMUNOHISTOCHEMICAL PROFILESNA CCC

CK7 + 40/40 (s) + 9/13 (s)CK20 + 23/40 (w) + 5/13 (var)CA-125 + 32/40 (mod) + 13/13 (s)RCC + 6/40 (s) NDCD10 + 9/40 (s) NDUroplakin - NDPAX 8 + +---------------------------------------------CEA - +PAX 2 + +-

PAX2+,Pax8+, Racemasa+

TRANSITIONAL CELL CARCINOMA, NESTED VARIANTTRANSITIONAL CELL CARCINOMA, NESTED VARIANT

Abnormal or complex architecture!

Muscularis propria invasion!Muscularis propria invasion!

• Benign lesion with no definitive premalignant potential

• NAs may recur, however, any recurrent tubulocystic or papillary lesion, especially with any degree of atypia in a woman, should raise the possibility of a CCC with deceptive benign features

• NA should be considered in the DDx of acinar proliferations in prostatic biopsies and TURPs

• There is no specific immunohistochemical profile to distinguish NA from its malignant mimics

NEPHROGENIC ADENOMANEPHROGENIC ADENOMA

RADIATION CYSTITISRADIATION CYSTITIS

PSEUDOEPITHELIOMATOUS HYPERPLASIA

RADIATION INDUCED ATYPIARADIATION INDUCED ATYPIA

CIS

RADIATION INDUCED ATYPIARADIATION INDUCED ATYPIA

CD44sp53 CK20

p53 CD44sCK20

CISCIS

ENDOMETRIOSIS OF THE ENDOMETRIOSIS OF THE URINARY BLADDERURINARY BLADDER

• Most common organ involved in the urinary tract• Typically affects women of reproductive age• It has been described in men with prostate cancer treated with estrogen therapy

• Catamenial exacerbations of symptoms• Secondary and significant complications• On cystoscopy: abnormalities present in 90% of women • Posterior wall and trigone more frequently involved• Rarely malignant transformation

ENDOMETRIOSIS

Endocervicosis Endocervicosis ofof the Urinary Bladderthe Urinary BladderClement PB, Young RH. Am J Surg Pathol 1992

• Women of reproductive age

• Common bladder symptoms including dysuria, frequency, hematuria, and pain

• Typically located in posterior wall or dome and forming a mass

• Involvement of muscularis propria by irregularly disposed benign endocervical glands

• 3/6 initially diagnosed as adenocarcinoma

MULLERIANOSIS OF MULLERIANOSIS OF THE URINARY BLADDERTHE URINARY BLADDER

ENDOCERVICOSIS ENDOCERVICOSIS OFOF THE THE URINARY BLADDERURINARY BLADDERDifferential Diagnosis

• Cystitis glandularis, intestinal type

• Urachal remnants

• Primary bladder adenocarcinoma

• Metastatic adenocarcinoma

Urachal Remnants

POSTOPERATIVE SPINDLE POSTOPERATIVE SPINDLE CELL NODULECELL NODULE

• First described by Proppe, Scully and Rosai (1984) in the genitourinary tract

• Typically associated with a previous history of surgery

• Clinical symptoms and cystoscopic findings often mimic a malignant neoplasm

• Myofibroblastic derivation• Benign clinical course, conservative treatment advised

INFLAMMATORY PSEUDOTUMORINFLAMMATORY PSEUDOTUMOR

• M > F: 3-60 (average 40) years• No previous history of surgery• Immunochemistry: Vimentin and cytokeratin + • EM: Myofibroblasts • DNA: Diploid • May recur but typically do not metastasize• Reactive vs neoplastic process (benign) but different from the so-called inflammatory myofibroblastic tumor of childhood

INFLAMMATORY PSEUDOTUMOR INFLAMMATORY PSEUDOTUMOR Worrisome features:

• Large polypoid intraluminal or intramural tumor

• Frequently gelatinous cut-surface

•Myxoid or edematous background with delicate

vasculature

• +/- infiltration into muscular wall/perivesical fat

• Variable cellularity and mitotic activity

• Necrosis deep in the muscularis propria (rare)

Myxoid/edematous and inflammatory background !

Associated necrosis!

POSTOPERATIVE SPINDLE CELL POSTOPERATIVE SPINDLE CELL NODULE VS INFLAMMATORY NODULE VS INFLAMMATORY

PSEUDOTUMORPSEUDOTUMOR

Only difference:

HISTORY OF INSTRUMENTATION

PSEUDOSARCOMATOUS MYOFIBROBLASTIC PROLIFERATIONS

Lara H, Am J Surg Pathol 2006,30:787-794

PSEUDOSARCOMATOUS PSEUDOSARCOMATOUS MYOFIBROBLASTIC PROLIFERATIONSMYOFIBROBLASTIC PROLIFERATIONS

Differential Diagnosis:

• Sarcomatoid carcinoma

• Carcinoma with pseudosarcomatous change

• Leiomyosarcoma

• Kaposis’s sarcoma

• Low-grade myofibroblastic sarcoma

Sarcomatoid Ca Leiomyosarcoma Infl Pseudotumor

SARCOMATOID CARCINOMASARCOMATOID CARCINOMA

• Controversy regarding nomenclature

• WHO definition: Biphasic malignant neoplasm exhibiting morphologic evidence of epithelial and mesenchymal differentiation (+/- heterologous elements)

• Previous history of carcinoma treated by radiation or chemotherapy is common

LEIOMYOSARCOMA OF THE LEIOMYOSARCOMA OF THE URINARY BLADDERURINARY BLADDER

• M>F (Average 50 yrs)

• Frequent myxoid degeneration

• Tumor cell necrosis at tumor-bladder wall interface

• No prominent microvasculature

• Only mild acute inflammatory infiltrate

• Frequently brisk mitotic activity

IMMUNOHISTOCHEMICAL PROFILESIMMUNOHISTOCHEMICAL PROFILES

SarcCA PSP LMS

Keratin + +/- -/+ (Focal)

CK5/CK6 + (25%) - -

34ßE12 + (25%) - -

EMA + -/+ -/+

SMA +/- (Focal) + +

Desmin - + +

S-100 - - -/+

ALK-1 - + -

p63 + (50%) - -/+

ALK-1

AE1/AE3 SMA

ALK expression not related to recurrences or muscle invasion

PSEUDOSARCOMATOUS PROLIFERATIONPSEUDOSARCOMATOUS PROLIFERATION

SARCOMATOID CARCINOMASARCOMATOID CARCINOMA

p63

CK 5/6 or HMCK p63

• UNUSUAL BENIGN LESIONS OF THE BLADDER MAY SUGGEST MALIGNACY

• CLINICAL HISTORY MAY BE OF HELP

• IHC MAY BE OF VALUE IN SOME CASES

CONCLUSIONS:

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