Case Report | Open Access
MALT Lymphoma of the Bladder: A Case Report and Review of the Literature
The presentation of a MALT lymphoma in the bladder is exceedingly rare. Furthermore, the optimal treatment of primary MALT confined to the bladder remains to be defined. Here, we report a case of a 65-year-old female with primary MALT lymphoma treated with definitive radiation therapy. The patient received a total dose of 30 Gy in 20 equal daily fractions to the bladder and tolerated the treatment well. In addition, we have extensively reviewed the relevant literature to better define the optimal management of this rare disease. In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy with excellent prognosis if detected at an early stage. For early stage disease, definitive radiation represents an excellent treatment modality with a minimal side-effect profile.
The majority of bladder cancers are epithelial in origin [1, 2]. Lymphomas of the urinary bladder are exceedingly rare and can be divided into (i) primary, a rare lymphoma arising in the urinary bladder with no evidence of lymphoma elsewhere, or (ii) secondary lymphoma of the urinary bladder associated with lymphoma at an extra vesicle site [3, 4]. Primary malignant lymphoma of the bladder accounts for less than 1% of neoplasms unlike secondary lymphoma, which is much more common [1, 2]. Of primary lymphomas of the bladder, mucosa associated lymphoid tissue lymphoma, or MALT, is the most prevalent histological subtype. The optimal treatment of primary MALT confined to the bladder remains to be defined. Here, we report a patient treated with definitive radiation and review the relevant literature to better define the optimal management of this rare disease.
2. Case Report
A 65-year-old female presented to her gynecologist after she noted a two-week history of spotting on toilet paper after urinating. She was referred to a urologist for further investigation of the bladder lesion. A transurethral resection of the bladder tumor (TURBT), with resection of the posterior bladder wall, right bladder wall, and bladder neck, was performed at an outside hospital. Initial pathology based on H&E stain and immunohistochemistry favored extra nodal marginal zone lymphoma with follicular colonization, with cells positive for CD20 and PAX-5 and negative for CD5 and CD10 (Figure 1). Laboratory evaluation including LDH, B2-microglobulin, serum immunofixation, and protein electrophoresis was all within normal limits. Subsequently, the patient underwent a PET/CT and bone marrow biopsy, and there was no evidence of any extra vesicular disease.
The patient was referred to radiation oncology to discuss the role of definitive radiation in her treatment regimen. Magnetic resonance imaging and repeat cystoscopy were recommended and performed to assess the presence of residual disease and were both negative. A well-healed biopsy area was noted on cystoscopy consistent with the site of original lesion. At this time, the patient’s hematuria was resolved and she denied any weight loss, fatigue, night sweats, or fevers. The patient had no history of recurrent sexually transmitted diseases. There was no lymphadenopathy, organomegaly, or abnormal findings on physical examination.
Based on patient’s lack of symptoms, negative imaging, and negative repeat cystoscopy, the patient was offered a course of close observation with serial cystoscopic evaluations versus definitive radiation given that the presence of microscopic disease could not be ruled out. She elected to proceed with radiation therapy. The patient received a total dose of 30 Gy in 20 equal daily fractions with a 4-field 3D-CRT plan utilizing PH16 MV photons. The adjacent normal structures were shielded with a multileaf collimator (MLC) (Figure 2). The patient tolerated radiation treatment well. She had no gastrointestinal, urinary, or gynecological toxicities during treatment and at short interval follow-up. Repeat evaluation 3 months following radiation with PET/CT revealed no evidence of disease and urine cytology was also negative.
Primary lymphoma of the bladder is a rare malignancy, with limited literature to guide therapy. The first ever reported case of bladder lymphoma was reported in the literature by Eve and Chaffey in 1885 [4–8]. There have been less than 100 cases described in the literature since [4, 9, 10]. The disease typically presents in the 6th decade of life with slight predominance in females [6, 10]. Since lymphoid tissue is not found in the urinary bladder, chronic inflammation is postulated as the origin. As such, most patients present with symptoms of chronic cystitis . However, similar to our patient, there have been many reported cases in which chronic cystitis and histological evidence of inflammation are lacking [4, 6, 11, 12]. The most common symptoms of lymphoma of the urinary bladder include weight loss, fatigue, hematuria, dysuria, nocturia, urinary frequency, and suprapubic or abdominal pain [4, 11, 12]. Table 1 contains a summary of basic patient demographics, presenting symptoms, treatments, and outcomes of all reported cases of primary MALT lymphoma of the bladder.
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CHOP: cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone.
R-CHOP: cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone, and rituximab.
ChlVP: chlorambucil, vincristine, and prednisolone.
TURBT: transurethral resection of bladder tumors.
NED: no evidence of disease.
There are many treatment options for nongastric MALT lymphomas: (i) observation (based on factors such as patient age, risk factors, and tumor grade, observation might be the best option ); (ii) surgery (complete excision or biopsy) (MALT lymphomas that are unifocal can be partially or completely removed with procedures like TURBT ); (iii) radiation (radiation, when given alone or after an excisional biopsy, has shown excellent local control and improved overall disease-free survival [10, 13–15]); (iv) chemotherapy (usually used when a patient presents with systemic involvement or secondary lymphoma of the bladder [16–18]); (v) targeted antibody therapy (anti-CD20 antibody (rituximab) has been used along with other modalities in systemic lymphomas [17, 19]); (vi) antibiotics (they are usually used in cases where there is a known bacterial origin such as H. pylori in the stomach). There have been rare cases where antibiotics were used for MALT lymphomas of the bladder .
The presentation of bladder MALT lymphoma is exceedingly rare; however, MALT lymphomas at other sites are common, especially in the GI tract, salivary gland, lung, Waldeyer’s ring, ocular adnexa, skin, thyroid, and breast. These lymphomas are highly radiosensitive. For localized disease, radiotherapy is the most appropriate treatment for organ preservation. It should be noted that, in patients of reproductive age, there is a risk of infertility with definitive radiation to the bladder secondary to the proximity of nearby reproductive organs. In these cases, maximal resection with TURBT may be the best treatment option when fertility is of concern. Chemotherapy and rituximab are reserved for secondary, recurrent, or disseminated disease [16–18, 21]. Al-Maghrabi et al. in 2001 identified four patients who received low dose radiotherapy for Stage IAE primary lymphoma of the bladder in a 30-year retrospective study. All four patients are alive and recurrence-free 2–13 years after treatment .
When considering radiation as a definitive monotherapy, staging becomes of utmost importance. 18F-FDG PET/CT, pelvic MRI, and bone marrow biopsy are used for initial disease staging and to rule out disseminated disease [1, 2, 10, 12]. As there was no evidence of disease in our patient’s imaging work-up and post-TURBT cystoscopy, she was presented with observation with cystoscopy at 3-4-month intervals versus radiation therapy with less frequent cystoscopy and imaging. The optimal follow-up strategy for patients with lymphoma of the bladder remains unknown. In our practice, once the patient achieves complete response on posttreatment imaging, no further imaging is indicated. Urine cytology should be performed at each visit and annual cystoscopy should be performed for the first 2-3 years.
In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy with excellent prognosis if detected at an early stage. For early stage disease, definitive radiation represents an excellent treatment modality with a minimal side-effect profile.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
- N. S. Curry, C. J. Chung, W. Potts, and N. Bissada, “Isolated lymphoma of genitourinary tract and adrenals,” Urology, vol. 41, no. 5, pp. 494–498, 1993.
- K. Arda, G. Özdemir, Z. Güneş, and H. Özdemir, “Primary malignant lymphoma of the bladder. A case report and review of the literature,” International Urology and Nephrology, vol. 29, no. 3, pp. 319–322, 1997.
- I. Matsuda, M. Zozumi, Y.-A. Tsuchida et al., “Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type with malakoplakia in the urinary bladder: a case report,” International Journal of Clinical and Experimental Pathology, vol. 7, no. 8, pp. 5280–5284, 2014.
- A. K.-G. Venyo, “Lymphoma of the urinary bladder,” Advances in Urology, vol. 2014, Article ID 327917, 19 pages, 2014.
- D. D. Cohen, C. Lamarre, L. Lamarre, and F. S. Fs, “Primary low-grade B-cell lymphoma of the urinary bladder: case report and literature review,” The Canadian Journal of Urology, vol. 9, no. 6, pp. 1694–1697, 2002.
- M. Ohsawa, K. Aozasa, K. Horiuchi, and A. Kanamaru, “Malignant lymphoma of bladder: report of three cases and review of the literature,” Cancer, vol. 72, no. 6, pp. 1969–1974, 1993.
- F. Eve, “Two cases of sarcoma of the bladder,” Transactions of the Pathological Society of London, vol. 36, article 284, 1885.
- W. Chaffey, “Lymphosarcoma of the bladder,” Transactions of the Pathological Society of London, vol. 36, p. 287, 1885.
- W. A. Mourad, S. Khalil, A. Radwi, A. Peracha, and A. Ezzat, “Primary T-cell lymphoma of the urinary bladder,” The American Journal of Surgical Pathology, vol. 22, no. 3, pp. 373–377, 1998.
- J. Al-Maghrabi, S. Kamel-Reid, M. Jewett, M. Gospodarowicz, W. Wells, and D. Banerjee, “Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder,” Archives of Pathology and Laboratory Medicine, vol. 125, no. 3, pp. 332–336, 2001.
- A. W. Bates, A. J. Norton, and S. Baithun I, “Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases,” Journal of Clinical Pathology, vol. 53, no. 6, pp. 458–461, 2000.
- R. H. W. Simpson, J. E. Bridger, P. P. Anthony, K. A. James, and I. Jury, “Malignant lymphoma of the lower urinary tract: a clinicopathological study with review of the literature,” British Journal of Urology, vol. 65, no. 3, pp. 254–260, 1990.
- Y. Takahara, H. Kawashima, Y.-S. Han et al., “Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder,” Acta Urologica Japonica, vol. 51, no. 1, pp. 45–48, 2005.
- G. Sufrin, B. Keogh, R. H. Moore, and G. P. Murphy, “Secondary involvement of the bladder in malignant lymphoma,” Journal of Urology, vol. 118, no. 2, pp. 251–253, 1977.
- K. Hatano, M. Sato, Y. Tsujimoto et al., “Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report,” Hinyokika Kiyo, vol. 53, no. 1, pp. 57–60, 2007.
- K. Ando, Y. Matsuno, Y. Kanai et al., “Primary low-grade lymphoma of mucosa-associated lymphoid tissue of the urinary bladder: a case report with special reference to the use of ancillary diagnostic studies,” Japanese Journal of Clinical Oncology, vol. 29, no. 12, pp. 636–639, 1999.
- Y. Kakuta, T. Katoh, J. Saitoh, K. Yazawa, M. Hosomi, and K. Itoh, “A case of primary mucosa-associated lymphoid tissue lymphoma of the bladder regressed after rituximab in combination with CHOP chemotherapy,” Acta Urologica Japonica, vol. 52, no. 12, pp. 951–954, 2006.
- M. Raderer, S. Wöhrer, B. Streubel et al., “Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma,” Oncology, vol. 70, no. 6, pp. 411–417, 2007.
- Y. Terasaki, H. Okumura, Y. Ishiura et al., “Primary mucosa-associated lymphoid tissue lymphoma of the urinary bladder successfully treated by radiotherapy and rituximab,” Rinshō Ketsueki, vol. 49, no. 1, pp. 30–34, 2008.
- M. Lucioni, M. Nicola, R. Riboni et al., “Antibiotic therapy-induced remission of bladder mucosa-associated lymphoid tissue (MALT) lymphoma carrying t(11;18)(q21;q21) apoptosis inhibitor 2-MALT1,” Journal of Clinical Oncology, vol. 31, no. 19, pp. e304–e306, 2013.
- N. A. Siddiqui, B. F. Branstetter IV, B. E. Hamilton et al., “Imaging characteristics of primary laryngeal lymphoma,” The American Journal of Neuroradiology, vol. 31, no. 7, pp. 1261–1265, 2010.
- M. Hughes, A. Morrison, and R. Jackson, “Primary bladder lymphoma: management and outcome of 12 patients with a review of the literature,” Leukemia and Lymphoma, vol. 46, no. 6, pp. 873–877, 2005.
- C. L. Kempton, P. J. Kurtin, D. J. Inwards, P. Wollan, and D. G. Bostwick, “Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma,” The American Journal of Surgical Pathology, vol. 21, no. 11, pp. 1324–1333, 1997.
- M. J. Fernandez Acenero, C. Martin Rodilla, J. Lopez Garcia-Asenjo, S. Coca Menchero, and J. Sanz Esponera, “Primary malignant lymphoma of the bladder. Report of three cases,” Pathology—Research and Practice, vol. 192, no. 2, pp. 160–165, 1996.
- J. Gallardo, C. Gamargo, M. Fodor, B. Comparini, P. Salman, and M. Yáñez, “MALT lymphoma of the bladder: report of a case,” Revista Médica de Chile, vol. 126, no. 2, pp. 199–201, 1998.
- K. Morita, F. Nakamura, Y. Nannya et al., “Primary MALT lymphoma of the urinary bladder in the background of interstitial cystitis,” Annals of Hematology, vol. 91, no. 9, pp. 1505–1506, 2012.
- H. D. Wazait, R. Chahal, S. K. Sundurum, G. N. Rajkumar, D. Wright, and M. M. Aslam, “MALT-type primary lymphoma of the urinary bladder: clinicopathological study of 2 cases and review of the literature,” Urologia Internationalis, vol. 66, no. 4, pp. 220–224, 2001.
- S. Sen, J. H. Macaulay, and S. L. Allford, “A case of cerebral arteriovenous malformation in pregnancy associated with MALT lymphoma,” Journal of Obstetrics and Gynaecology, vol. 30, no. 3, pp. 308–310, 2010.
- R. W. Tsang, M. K. Gospodarowicz, M. Pintilie et al., “Stage I and II malt lymphoma: results of treatment with radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 50, no. 5, pp. 1258–1264, 2001.
- H. Takahashi, H. Shimazaki, T. Oda et al., “Malignant lymphoma case with urinary cytology mimicking that of urothelial carcinoma,” Cytopathology, vol. 24, no. 6, pp. 412–414, 2013.
- Y. Ueno, H. Sakai, T. Tsuruta, and M. Wajiki, “Mucosa-associated lymphoma of the bladder with relapse in the stomach after successful local treatment,” Hinyokika Kiyo, vol. 53, no. 8, pp. 575–579, 2007.
- J. E. M. Haddad-Lacle, C. J. Haddad, and B. Villas, “A rare urinary bladder tumour,” BMJ Case Reports, 2014.
- T. R. Szopiński, I. Sudoł-Szopińska, T. Dzik, A. Borówka, B. Dembowska-Bagińska, and D. Perek, “Incidental sonographic detection of mucosa-associated lymphoid tissue lymphoma of the urinary bladder found in a very young woman: report of a case,” Journal of Clinical Ultrasound, vol. 39, no. 4, pp. 233–235, 2011.
- K. G. Maninderpal, F. H. Amir, H. A. R. Azad, and K. S. Mun, “Imaging findings of a primary bladder maltoma,” British Journal of Radiology, vol. 84, no. 1005, pp. e186–e190, 2011.
- K. Kawakami, K. Oka, M. Kato, and H. Shiku, “Whole-bladder irradiation and doxorubicin-containing chemotherapy as successful treatment for a primary mucosa-associated lymphoid tissue lymphoma of the bladder,” International Journal of Hematology, vol. 72, no. 3, pp. 346–348, 2000.
- J. P. Tasu, D. Geffroy, L. Rocher et al., “Primary malignant lymphoma of the urinary bladder: report of three cases and review of the literature,” European Radiology, vol. 10, no. 8, pp. 1261–1264, 2000.
- C. Painemal Duarte, J. Gallardo, J. P. Valdebenito, C. Gamargo, B. Rubio, and H. Harbst, “MALT lymphoma of the bladder. Report of a case,” Archivos Españoles de Urología, vol. 54, no. 10, pp. 1138–1140, 2001.
- K. Mizuno, S. Nakanishi, T. Sakatani et al., “A case of primary mucosa-associated lymphoid tissue-type lymphoma of the urinary bladder that progressed after antibiotic therapy,” Hinyokika kiyo, vol. 59, no. 4, pp. 239–242, 2013.
- J. Bacalja, M. Ulamec, D. Rako et al., “Persistence of primary MALT lymphoma of the urinary bladder after rituximab with CHOP chemotherapy and radiotherapy,” In Vivo, vol. 27, no. 4, pp. 545–549, 2013.
- E. K. Mayer, S. Undre, D. C. Cohen, M. M. Walker, J. A. Vale, and A. Patel, “‘An unusual urological tumour’: above the collar and below the belt,” Case Reports in Oncological Medicine, vol. 2012, Article ID 480826, 3 pages, 2012.
- J. van den Bosch, R. F. Kropman, P. Blok, and P. W. Wijermans, “Disappearance of a mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder after treatment for Helicobacter pylori,” European Journal of Haematology, vol. 68, no. 3, pp. 187–188, 2002.
- M. Fujimura, K. Chin, N. Sekita et al., “Regression of mucosa-associated lymphoid tissue lymphoma of the bladder after antibiotic therapy: a case report,” Acta Urologica Japonica, vol. 54, no. 12, pp. 783–786, 2008.
- T. Terada, “Primary CD5-positive mucosa-associated lymphoid tissue lymphoma of the urinary bladder,” Annals of Diagnostic Pathology, vol. 15, no. 5, pp. 382–384, 2011.
- S. M. Kröber, C. Aepinus, P. Ruck, H.-K. Müller-Hermelink, H.-P. Horny, and E. Kaiserling, “Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach,” Journal of Clinical Pathology, vol. 55, no. 7, pp. 554–557, 2002.
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