Case Reports in Hematology
Volume 2015 (2015), Article ID 934374, 7 pages
http://dx.doi.org/10.1155/2015/934374

Case Report

MALT Lymphoma of the Bladder: A Case Report and Review of the Literature

Prashant Vempati,¹ Miriam A. Knoll,² Mahfood Alqatari,³ James Strauchen,³ Adriana K. Malone,⁴ and Richard L. Bakst²

¹Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
²Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
³Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
⁴Department of Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

Received 9 July 2015; Accepted 12 August 2015

Academic Editor: Marie-Christine Kyrtsonis

Copyright © 2015 Prashant Vempati et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

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.

1. Introduction

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.

(a)

(b)

(c)

(d)

Figure 1: (a) Low power images of H&E stain show infiltration of the bladder wall by small plasmacytoid lymphocytes. (b) High power images of H&E stain show infiltration of the bladder wall by small plasmacytoid lymphocytes. (c) CD20 stain shows positive cells. (d) PAX-5 stain shows diffusely positive cells.

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.

(a)

(b)

(c)

Figure 2: 3D conformal radiation therapy of MALT lymphoma of the bladder with dose distributions depicted in the sagittal (a), axial (b), and coronal (c) planes.

3. Discussion

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 [9]. 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.

Table 1: Characteristics of reported cases of primary MALT lymphoma of the bladder on PubMed as of June 2015.

Author
Age
Sex
Presenting symptom
Treatment
Follow-up (Months)
Outcome

Hughes et al., [22]
81
Female
Hematuria
Diathermy TURBT
12
NED

Ando et al., [16]
77
Female
Urinary retention
TURBT
36
NED

Kempton et al., [23]
64
Female

Partial cystectomy
144
Died of unknown cause

Fernandez Acenero et al., [24]
73
Female
Dysuria, Back pain
Chemotherapy
8
Died of unknown cause

Fernandez Acenero et al., [24]
50
Female
Fever
Chemotherapy
60
NED

Fernandez Acenero et al., [24]
75
Female
Hematuria, dysuria and Breast carcinoma
Chemotherapy
9
NED

Gallardo et al., [25]
70
Female
Hematuria, Dysuria, Malaise and weight loss
Chemotherapy
24
NED

Morita et al., [26]
68
Female
persistent interstitial cystitis
Chemotherapy [Rituximab]

NED

Wazait et al., [27]
65
Female
Hematuria, dysuria and recurrent UTI’s
Chemotherapy [CHOP]
36
NED

Hughes et al., [22]
77
Male
Hematuria
Chemotherapy [ChID]
48
NED

Hughes et al., [22]
28
Male
Hematuria
Chemotherapy [ChIVP]
120
NED

Kakuta et al., [17]
84
Female
General fatigue and weight loss
Chemotherapy [R-CHOP]

Sen et al., [28]
31
Female
Incidental finding - Pregnancy
Postpartum Chemotherapy

Kempton et al., [23]
79
Female

Radiation
24
Died of Myocardial infarction

Al-Maghrabi et al., [10]
64
Female
Hematuria, and recurrent UTI
Radiation
156
NED

Al-Maghrabi et al., [10]
69
Female
Treatment resistant UTI
Radiation
60
NED

Al-Maghrabi et al., [10]
72
Female
Hematuria and recurrent UTI
Radiation
36
NED

Al-Maghrabi et al., [10]
62
Male
Hematuria
Radiation
24
NED

Tsang et al., [29]

Radiation

NED

Tsang et al., [29]

Radiation

NED

Tsang et al., [29]

Radiation

NED

Hughes et al., [22]
76
Female
Hematuria
Radiation
24
NED

Hughes et al., [22]
66
Female
Recurrent UTI
Radiation

Deceased

Takahara et al., [30]
85
Female
Hematuria
Radiation

NED

Hatano et al., [15]
84
Female
Hematuria and recurrent UTI
Radiation
12
NED

Kempton et al., [23]
73
Female

Fulguration and Radiation
120
Died of unknown cause

Kempton et al., [23]
27
Female

Tumor resection and Radiation
480
Died of fibrosarcoma

Kempton et al., [23]
45
Male

Segmental resection and Radiation
312
Died of unknown cause

Kempton et al., [23]
50
Female

Segmental resection and Radiation
240
NED

Ueno et al., [31]
64
Female
Incidental finding
TURBT and Radiation
19
Recurrence Stomach

Haddad-lacle et al., [32]
54
Male
Low back pain, incidental bladder mass
TURBT and Radiation
36
NED

Wazait et al., [27]
70
Female
Hematuria
TURBT-1 yr recurrence, Chemotherapy on recurrence
60
NED

Szopiński et al., [33]
17
Female
Incidental finding
TURBT and Chemotherapy
24
NED

Maninderpal et al., [34]
65
Female
Chronic suprapubic mass, nausea and feeling unwell
TURBT and Chemotherapy
3
Died of Sepsis

Matsuda et al., [3]
78
Female
Refractory Cystitis and renal dysfunction
TURBT and Chemotherapy [rituximab]

Kawakami et al., [35]
27
Male

Radiation and Chemotherapy [doxorubicin]
18
NED

Tasu et al., [36]
75
Female
Hematuria
Radiation and Chemotherapy [cyclophosphamide]
36
NED

Painemal et al., [37]
70
Female
Hematuria, Dysuria, Malaise and weight loss
Radiation and Chemotherapy
48
NED

Hughes et al., [22]
82
Female
Hematuria
Radiation + Chemotherapy [ChIVP]

Deceased

Terasaki et al., [19]
64
Female
General malaise and anemia
Radiation and Chemotherapy [Rituximab]
14
NED

Mizuno et al., [38]
72
Female
Hematuria and recurrent cystitis
TURBT, Radiation and Chemotherapy [rituximab]

Bacalja et al., [39]
48
Male
Incidental finding
TURBT, Radiation and Chemotherapy [R-CHOP]
5
Remission

Mayer et al., [40]
70
Male
Bladder mass with scalp metastasis
Chemotherapy and Radiation for scalp and brain
14
Died of Brain Metastasis

van den Bosch et al., [41]
59
Male
Hematuria
triple therapy [patient denied radiation]
36
NED

Fujimura et al., [42]
69
Female
Hematuria and anemia
Antibiotics and H. pylori therapy
24
NED

Terada, [43]
88
Female
Hematuria
Antibiotics
6
Markedly reduced tumor size

Lucioni et al., [20]
72
Female
Persistent dysuria
Antibiotics
6
NED

Bates et al., [11]
66
Female
Bladder mass

12
NED

Bates et al., [11]
79
Female
Hematuria

Bates et al., [11]
59
Female
Untreated solid necrotic tumor

36
NED

Kröber et al., [44]
57
Male
Obstructive dysuria

Takahashi et al., [30]
71
Female
Hematuria

Authors do not have access to this information.

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 [11]); (ii) surgery (complete excision or biopsy) (MALT lymphomas that are unifocal can be partially or completely removed with procedures like TURBT [11]); (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 [20].

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 [10].

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.

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