Path. Res. Pract. 192, 160-163 (1996)
Teaching Cases
Primary Malignant Lymphoma of the Bladder Report of Three Cases M. J. Fernandez Aceiiero, C. Martin Rodilla, J. L6pez GarclaAsenjo, S. Coca Menchero1 and J. Sanz Esponera Department of Surgical Pathology (Unidad I, Prof. Sanz Esponera) Hospital Universitario Clfnico de San Carlos and 1Hospital del Aire, Madrid, Spain
SUMMARY Primary malignant lymphoma of the bladder is a rare tumour. In a recent literature search only 70 cases have been found since 1885. Most of these tumours were low grade B-cell non Hodgkin's lymphomas and only 20 % were high grade neoplasms. This tumour usually appears in women between 20 and 85 years (median 64 yr.) of age. 20 % of them have antecedents of chronic cystitic. Some authors have considered that some of the primary malignant lymphomas of the bladder arise from the mucosaassociated lymphoid tissue (MALT), therefore acting like MALT lymphomas which affect the gastrointestinal tract, the salivary glands or the thyroid. We report three additional cases of primary malignant lymphoma of the bladder, two of high grade, and discuss the histological criteria that support their MALT nature.
Introduction Primary malignant lymphoma of the bladder is a rare tumour. In the most recent review of the literature, reported in 19931, only 70 cases were found. Most of these were low grade non Hodgkin's lymphoma of B-cell type. Only 20 % were high grade and only 3 cases, Hodgkin's disease l , 2. Immunohistochemistry, although performed in only 20 % of the reported cases, the B-cell nature of the tumour was confirmed in all cases. We report three new cases of primary malignant lymphoma of the bladder diagnosed in our department between 1975 and 1994. Two of our cases are high grade large cell tumours, and in three cases immunohistochemistry confirms their B-cell nature. Report of the Cases The main features of these cases are highlighted in Table 1. 0344-0338/96/0192-0160$3.50/0
Clinical Findings
All the patients were women, aged 73, 50 and 75. One of them (case 3) had antecedents of breast carcinoma. Two were consulted for pain and dysuria and the other (case 2) for fever of unknown origin. Image Technics
In the three cases, a CT scan showed the presence of a mass in the wall of the bladder, from which a transurethral biopsy was obtained. Clinical diagnosis was in two cases transitional carcinoma and, in case 3, metastasis to the bladder from breast carcinoma. Histological Findings
In case 1 the resection of the mass demonstrated the existence of a lymphoid neoplasia which affects the mucosa and the surrounding connective tissue. In some areas we still found a transitional epithelial lining that showed ulceration and infiltration by lymphocytes. © 1996 by Gustav Fischer Verlag, Stuttgart
Primary Malignant Lymphoma· 161 Table 1. Summary of the cases Sex
Age
Clinical findings
Case 1
F
73
Case 2
F
50
Case 3
F
75
Hight grade cen- LCA (+) MTl (-) Death 8 mo. later troblastic lympho- L26 (+) UCHLl unrelated cause. (-) MB2 (+) rna No recurrence in bladder. Lymphoma of the thyroid. CT scan: mass lat- Low grade malig- MB2 (+) L26 (+) Alive and free of Fever eral wall of bladder nant lymphoma disease 5 yr. later Kappa (+) Breast carcinoma CT scan: mass in Hight grade cen- L26 (+) MB2 (+) Alive and free of Hematuria Dysuria the bladder troblastic lymphodisease after 9 mo. rna Pain left lumbar area Dysuria
Image technique
Histological findings
Immunohistochemistry
Outcome
CT scan: mass in the bladder
The proliferating cells were organized in cohesive clusters with scattered macrophages between them, giving the tumor a "starry-sky" pattern. The cells were of intermediate size (9 -11 Il), with sparse cytoplasm and a big oval nucleus with a highly condensed coarse chromatin that fades the existence of two or more nucleoli (Fig. 1). There were many mitotic figures and small areas of necrosis. Our diagnosis was high grade centroblastic lymphoma. Case 2 showed a lymphoid neoplasm with a diffuse pattern of growth. The tumor was composed of small centrocyte-like cells, some with plasmacytic differentiation. There were several reactive germinal centers, some of them showing colonization by centrocyte-like cells (Fig. 2). The transitional epithelium was focally infiltrated by small lymphocytes (that stain with immunohistochemical markers for T-cells, Fig. 3). Our diagnosis was low grade malignant lymphoma. Microscopically, case 3 showed a diffuse proliferation of lymphoid cells of intermediate or big size with an oval nucleus, fine chromatin and peripherycally located nucleoli. They show scant basophylic cytoplasm. Our diagnosis was high grade centroblastic lymphoma.
Immunohistochemistry In the three cases immunohistochemistry showed
positivity for LCA, L26 (Fig. 4), MB2 and negativity for MTI and UCHLl confirming the B-cell nature of the lesions. Case 2 showed restricted expression of Kappa light chain. Cytokeratin was negative.
Out-come Patient 1 was reassessed and no evidence of tumour was elsewhere found. She received systemic chemotherapy and the mass disappeared. Eight months later, the patient was readmitted because of a fracture of the pelvic bones. She died two days after surgery due to pulmonary thromboembolism. The autopsy confirmed the cause of death. Sections from different areas of the bladder showed a diffuse thickening of the wall, but no malignant lymphoid cells. However, sections of
the thyroid gland showed a multifocal infiltration of lymphoid cells whose morphological features were similar to those of the primary malignant lymphoma described in the bladder. We did not find tumour elsewhere. Neither patient 2 nor patient 3 had evidence of tumour elsewhere. Both received chemotherapy and today, five years (case 2) and nine months after treatment, they are alive and free of disease. Discussion The incidence of secondary involvement of the bladder in the course of Iymphoproliferative diseases ranges from 7 % to 13 % according to different authors 3 • Nevertheless, primary malignant lymphoma of the bladder is extremely rare, with only 70 cases reported since 1885 1 • Some authors have reported a striking preponderance in women (male to female ratio 1: 6.5) I. The age ranges from 20 to 85 years with a mean of 64 years. The most commonly presented clinical symptoms are hematuria and dysuria, identical to those of the more frequent carcinoma of the bladder, although the association hematuria-polaquiuria seems to be slightly more frequent in malignant lymphoma of the bladder. At cystoscopy the most cO!llmon macroscopic findings are solitary masses 1 usually located in the lateral walls of the bladder. Histologically, most of these tumours are non Hodgkin's Iymfhomas 1,4,5 with only three cases of Hodgkin's disease l , . Most of these neoplasms are low grade B-cell lymphomas, although in only 20 % of the reports had immunohistochemistry been performed l , 4. Only 20 % of the cases were high grade diffuse large cell malignant lymphomas1,6, a fact which differentiates this tumour from other kinds of extranodal lymphomas among which high grade lesions are usually more than 50 % of the cases 7 • Some authors have postulated that some of the primary malignant lymphomas of the bladder arise from
Fig. 1. Diffuse growth of malignant lymphoid cells, most of which show several nucleoli (H-E, x 400).
Fig. 3. Transitional epithelium focally infiltrated by small lymphocytes (H-E, x 100).
Fig. 2. A reactive germinal center showing colonization by centrocyte-like cells (H-E, x 400).
Fig. 4. Positivity with L-26 (Immunohistochemistry for L26, x 400).
Primary Malignant Lymphoma· 163
the mucosa-associated lymphoid tissue (MALT). The concept of MALT lymphomas was introduced in 1983 by Isaacson et al. 8 for low grade malignant lymphomas of B-cell origin affecting the gastrointestinal tract. They show several typical features: they are tumours composed of centrocyte like cells with abundant clear cytoplasm that infiltrate the mucosal epithelium (forming lymphoepitheliallesions) and colonize the reactive germinal centers frequently present in this lesion. Besides, some of the neoplastic cells show signs of plasmacytic differentiation. Nowadays the concept of MALT lymphoma has evolved and includes all the lymphomas arising from organs in which there are lymphoid cells associated with ductal or epithelial structures. In this sense today we consider that most lymphomas affecting the thyroid 10, the salivary glands!!, the orbit and the thymus 12 are MALT lymphomas. Only two reports have specifically considered bladder lymphoma as a MALT lymphoma 9, 13 because of its histological features and its biological behaviour. It is not yet well known whether there is lymphoid tissue in the bladder or not. On one hand, some authors have denied that bladder lymphomas could be of MALT nature because only 22 % of the patients refer antecedents of chronic cystitis and they regard this condition a necessary precursor of MALT lymphoma 4 • On the other, some authors think that this neoplasm arises from the lymphoid tissue of the embryonic cloaca, from which the bladder derives 9 • We agree with Isaacson and other authors who think that it is more likely that these tumours arise from acquired lymphoid follicles. In one of the cases we found lymphoid follicles inside the tumour, although the patient had no antecedents of chronic cystitis. Pawade et al. have seen lymphoepitheliallesions in only one of the five cases they report 11 , in a patient showing chronic cystitis glandularis. We consider that malignant lymphomas of the bladder share with other MALT lymphomas, apart from the characteristic histological features, an extremely good prognosis (overall supervivence of 72 %4) and a tendency to remain localized in the site of origin for long periods of time with a low risk of dissemination. Besides, one of our patients showed recurrence of the tumour in another extranodal site, the thyroid, a well known feature of MALT lymphomas which usually recur in another MALT territory (case 1). We report three new cases of this very rare entity that can be easily confused with inflammatory lesions. A misdiagnosis of this tumour can allow the dissemination or transformation to a high grade lesion because of the delay in the treatment. We think that it is very important to diagnose this tumour and exclude the possibility of a carcinoma (there have been reports of the
association of lymphoma and carcinoma of the bladder l4 , 15, and some reports of carcinomas simulating malignant lymphomas I6 ). Some authors think that there would be no need for radical surgery in primary malignant lymphoma of the bladder, although that is the most frequent treatment reported in the literature for these tumours. Perhaps local radiotherapy or chemotherapy (successful in our patients) is sufficient treatment. References 1 Ohsawa M, Aozasa K, Horiuchi K, Kanamuru A (1993) Malignant lymphoma of the bladder. Report of three cases and review of the literature. Cancer 72: 1969 -1974 2 Jones M (1989) Primary Hodgkin's disease of the urinary bladder. Brit J. Urol 63: 438 3 Sufrin G, Keogh B, Moore RH, Murphy GP (1977) Secondary involvement of the bladder in malignant lymphoma. J Uro1118: 251-253 4 Simpson RHW, Bridger JE, Anthony PP, James KA, Jury I (1990) Malignant lymphoma of the lower urinary tract. A clinicopathological study with review of the literature. Br J Urol 65: 254-260 5 Siegelbaum MH, Edmonds P, Seidmon EJ (1986) Use of immunohistochemistry for identification of primary malignant lymphoma of the bladder. J Urol 136: 1074-1076 6 Miyake 0, Tsujihata M, Itoh H, Wakatsuki A, Itatani H (1994) Nippon Hyniokika Gakkai Zasshi 85: 668 - 671 7 Bhansali SK, Cameron KM (1960) Primary malignant lymphoma of the bladder. Brit J Urol 32: 440-454 8 Isaacson P, Wright DH (1983) Malignant lymphoma of mucosa associated lymphoid tissue. A distinctive type of Bcell lymphoma. Cancer 52: 1410-1416 9 Pawade J, Banerjee SS, Harris M, Isaacson P, Wright D (1993) Lymphomas of mucosa associated lymphoid tissue arising in the urinary bladder. Histopathology 23: 147 -151 10 Anscombe AM, Wright DH (1985) Primary lymphoma to the thyroid. A tumor of mucosa-associated lymphoid tissue: review of seventy-six cases. Histopathology 9: 81- 97 11 Hyjek E, Smith W, Isaacson PG (1988) Primary celllymphoma of salivary glands and its relationship to myoepithelial sialadenitis (MESA). Hum Pathol 19: 766 - 776 12 Isaacson PG, Chan JKC, Tang C, Addis BJ (1990) Low grade B-ceillymphoma of mucosa-associated lymphoid tissue arising in the thymus. Am J Surg Pathol14: 342-351 13 Kuhara H, Tamura Z, Suchi T, Hattori R, Kinuwaka T (1990) Primary malignant lymphoma of the urinary bladder. A case report. Acta Pathol Jpn 40: 764-769 14 Aquilina IN, Bugeja TJ (1974) Primary malignant lymphoma of the bladder: case report and review of the literature. J Uro1112: 64-65 15 Stitt RB, Colapinto V (1966) Multiple simultaneous bladder malignancies: primary lymphosarcoma and adenocarcinoma. J Urol 96: 733 - 736 16 Zukerberg LR, Harris NL, Young RH (1991) Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases. Am J Surg PathoI15:569-576
Received January 18, 1995 . Accepted in revised form October 9, 1995
Key words: Malignant lymphoma - Bladder - MALT lymphoma - Non-Hodgkin's lymphoma - Hodgkin's lymphoma - Large cells tumours - Chronic cystitis - Carcinoma Dr. M.
J.
Fernandez Acenero, CfTutor, 48, 2°_B, 28008 Madrid, Spain