PATHOLOGICA 2005;97:338-340
CASO
CLINICO
Micropapillary transitional cell carcinoma
of the urinary bladder: report of two cases
Carcinoma micropapillare a cellule transizionali della vescica urinaria:
report di due casi
R.S. DHOUIB, I. ABBES, K. MRAD, S. SASSI, A. LEILA, M. DRISS, R. SALAH 1, K.B. ROMDHANE
Histopathology Departement, “Salah Azaïez” Institute, Tunis, Tunisia; 1 Departement of Surgery, Section of Urology, “Zaghouan”
Hospital, Tunis, Tunisia
Keys words
Urinary bladder • Transitional cell carcinoma •
Micro papillary variant
Summary
Parole chiave
Vescica • Carcinoma a cellule transizionali •
Variante micropapillare
Riassunto
Micropapillary carcinoma is an uncommon variant of urothelial
carcinoma with apparent high metastatic potential. The reported
cases in the literature were associated with high grade and stage
of disease at presentation and a poor prognosis. Micropapillary
carcinoma is considered a tumor with an aggressive behavior,
even though the morphology may be deceptive. The presence of
a micropapillary carcinoma component in bladder biopsies
should alert the urologists to the potential of higher stage disease
and deep biopsies should be obtained. Two cases of micropapillary carcinoma of the urinary bladder were presented. A 71-yearold woman and a 68-year-old man presented with urinary symptoms. Cystoscopy revealed a papillary tumor on the bladder wall
in both cases. Pathologic examination of transurethral resection
specimen showed an invasive micropapillary carcinoma; small
solid nests lying in small clear spaces that were not stained with
antibody CD34. Thus, the lacunar histological pattern did not appear to represent invasion of vascular spaces. Only one case
showed an association with urothelial carcinoma. No case
showed muscle invasion. No recurrence or metastasis were observed after the initial diagnosis in the two cases.
Il carcinoma micropapillare è una variante poco comune del
carcinoma uroteliale con elevato potenziale metastatico. I casi
riferiti in letteratura presentano grado e stadio avanzato della
malattia alla diagnosi e prognosi sfavorevole. Il carcinoma
micropapillare è considerato pertanto una neoplasia aggressiva, anche a fronte di una morfologia ingannevole. La presenza
di una componente di carcinoma micropapillare in biopsie
vescicali deve allertare l’urologo riguardo la possibilità di una
malattia in stadio avanzato. Vengono presentati due casi di carcinoma micropapillare della vescica, rispettivamente riguardanti una donna di 71 anni ed un uomo di 68 anni, entrambi
con sintomatologia urinaria. La cistoscopia ha evidenziato in
entrambi la presenza di neoplasia papillare. L’esame istologico
di campioni ottenuti per via transuretrale ha dimostrato trattarsi di carcinoma micropapillare invasivo con evidenza di piccoli nidi solidi all’interno di spazi chiari risultati negativi alle
indagini immunoistochimiche con anticorpo anti-CD34. Tale
pattern lacunare è stato pertanto dimostrato non rappresentare
un quadro di invasione vascolare. Solo uno dei due casi era
associato ad un carcinoma uroteliale. Nessuno dei due casi presentava invasione muscolare. In entrambi non si è verificata né
recidiva né metastasi dopo la diagnosi iniziale.
Introduction
cidence of 1.5% 1. We report two additional cases detected in bladder biopsy specimens.
Micropapillary architecture has been recognized in carcinomas involving different organs such as ovary, breast, endometrium, thyroid gland and urinary bladder. It
is nearly always associated with high disease stage at
presentation and aggressive clinical course 1. The micropapillary variant of urothelial carcinoma (MUCC)
of the urinary bladder was first described in 1994 by
Amin et al. 1. In this report, 18 cases of MUCC were
identified prospectively and retrospectively with an in-
Case n. 1
A 71-year-old woman, initially presented with gross hematuria, dysuria, pelvic pain and burning micturition.
Cystoscopy revealed a papillary tumour on the posterolateral bladder wall. Transurethral resection of the neoplasm was performed, yielding fragments measuring
Corrispondenza
Rakrouki Salah, Zaghouan Hospital, Tunis, Tunisia - Tel. +216
71 577848 - Fax +216 71 574725 - E-mail: [email protected]
MICROPAPILLARY BLADDER CANCER
Fig. 1. Small solid nests and micro papillae lying in small clear
spaces. The nuclei were slightly increased in size, exhibiting slight pleomorphism (HE x 400).
339
diagnosis of low grade urothelial cell carcinoma with
micropapillary architecture invading the lamina propria
was advanced. The patient had undergone adjuvant radiation therapy. To date, no recurrence or metastasis were observed six months after the initial diagnosis.
Case n. 2
20x15x15 mm altogether. Preoperative computed tomograhpy showed a right pyelo-calicial expansion above
urinary bladder obstruction. Pathologic examination revealed small solid nests and micro papillae lying in small
clear spaces. Marked atypia was absent. The nuclei were slightly increased in size, exhibited slight pleomorphism and were mildly hyperchromatic. The underlying stroma was desmoplastic. No vascular invasion
was noted in lamina propria (Fig. 1). Immunohistochemistry was performed using the avidin-biotin-peroxidase complex method. Tumoral cells were stained with
both monoclonal antibody to cytokeratin 7 CK7 (1/50
dilution, Dako corporation) and cytokeratin 20 CK20
(1/50 dilution, Dako corporation) (Fig. 2). The lacunar
spaces were not stained with CD34 (prediluted, Dako corporation) indicating their nonvascular origin (Fig. 2). A
A 68-year-old man presented with gross hematuria. Cystoscopy revealed a papillary tumour on the posterior
bladder wall. Transurethral resection demonstrated non
invasive low grade papillary urothelial carcinoma. The
patient received a 6-week course of weekly intravesical
instillation of BCG (bacillus Calmette-Guerin). The patient returned five months after initial biopsy with gross
hematuria. Repeat resection showed a recurrent tumour
on the lateral bladder wall. Microscopic examination revealed a superficial papillary growth of tumour cells and
a deep pattern of tight infiltrating clusters of micro papillary aggregates residing within lacunae. Marked cytologic and high mitotic activity were noted. The specimen
did not contain the muscle layer. The tumour cells were
stained with both monoclonal antibody to CK 7 and CK
20. A diagnosis of high grade papillary urothelial carcinoma with micropapillary component and extensive invasion of the lamina propria was advanced. The patient
unberwent an ulterior 6 week course of weekly intravesical BCG. To date, no recurrence or metastasis were observed three months after the initial diagnosis.
Discussion
The micropapillary variant of transitional cell carcinoma of the urinary bladder is exceedingly rare. It is of-
Fig. 2. Left: tumour cells are stained with monoclonal antibody to CK 7 (x 400). Middle: tumour cells are stained with monoclonal antibody
to CK 20 (HE x 400). Right: the lacunar spaces are not stained with CD34 (x 400).
R.S. DHOUIB ET AL.
340
ten associated with conventional urothelial carcinoma.
There is a male predominance and patients age range
from fifth to the ninth decade with a mean age of 66
years 5. The neoplasm has no specific clinical complaints but is histologically well defined 1-3. Three
morphologic features of this variant were of note 2. First, it was characterized by a filiform architecture in the
surface component and by small, tight aggregates of tumour cells in invasive and metastatic component. Second, psammoma bodies were conspicuously absent 4.
Third, the tumour cells were predominantly aggregated
in lacunae at random intervals within the tissue 2.
Although, initially thought to represent vascular invasion, factor VIII and CD31 staining revealed that the
majority of these lacunae were not vascular but represented artifactually retracted tissue spaces identical to
those seen in other micropapillary tumours 1 2. At least
focal vascular invasion has been shown in all cases reported by Amin et al. 2. Seventeen cases had muscle invasive disease at cystectomy 2. All 18 cases in the original report had advanced disease (stage B or higher)
and all were histological grade 3 2. The micropapillary
pattern in the bladder appears to correlate with higher
disease stage at presentation and a more aggressive clinical course 1-3. Micropapillary carcinoma is considered
a tumor with an aggressive behavior, even though the
morphology may be deceptive. Moreover, in all patients with metastases (8 cases), the metastatic foci were composed predominately of micropapillary carcinoma. Immunohistochemical studies in one large series
disclosed immunoreactivity of the micropapillary carcinoma in all cases for epithelial membrane antigen
EMA, CK7, CK20 et Leu M1. CEA was positive in 13
of 20 cases 5 6. This immunohistochemical profile allows distinction with metastatic localisation of ovary
papillary carcinoma. Urothelial carcinoma with micropapillary component must be considered as primary
especially in males and women with normal gynaecologic examination. Image analysis shows aneuploidy 5.
Maranchie JK et al demonstrated no significant p53 abnormalities and decreased normal E-cadherin expression that is responsible for cell dispersion, dedifferentiation and invasive potential 1. He concluded that micropapillary carcinoma seems to have the ability to disrupt and replace the normal stromal matrix to achieve
rapid non endothelial extension 1. In conclusion, micropapillary carcinoma is an uncommon variant of
urothelial carcinoma with apparent high metastatic potential. The presence of a micropapillary carcinoma
component in bladder biopsies should alert the urologists to the potential of higher stage disease and deep biopsies should be obtained 2 4.
References
4
1
2
3
Maranchie JK, Bouyoune BT, Zhang PL, O’Donnell M, Summerhayes IC, Dewolf WC. Clinical and pathological characteristics of micropapillary transitional cell carcinoma: a highly aggressive variant. J Urol 2000;163:748-51.
Amin MB, Ro JY, El Sharkawy T, Lee KM, Troncoso P, Silva EG,
et al. Micropapillary variant of transitional cell carcinoma of urinary bladder. Am J Surg Pathol 1994;18:1224-32.
Lopez JI, Elorriaga K, Imaz I, Bilbao FJ. Micropapillary transitionnel cell carcinoma of urinary bladder. Histopathol
1999;34:561-2.
5
6
Vang R, Abrams J. A micropapillary variant of transitional cell
carcinoma arising in the ureter. Arch Pathol Lab Med
2000;124:1347-8.
Eble JN. World Health Organisation Classification of tumours.
Pathology and Genetics of Tumors of the Urinary System and male Genital Organs. IARC Press Lyon 2004.
Johansson SL, Borghede G, Holmang S. Micropapillary bladder
carcinoma: A clinicopathological study of 20 cases. J Urol
1999;161:1798-802.