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Micropapillary Urothelial Carcinoma (MUC) of the Upper Urinary Tract: An Underreported but Aggressive Variant of Urothelial Carcinoma

We report 3 patients with MUC of the upper urinary tract who were evaluated and treated at our center between 2009 and 2011.

Authors: Xiao-hua Zhang1,Zhou-jun Shen1,Xiu-ling Wu2,Zhixian Yu3

  1. Department of urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
  2. Department of pathology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325000, China
  3. Department of urology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325000, China

Corresponding Author: Zhixian  Yu,   Department of urology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325000, China. E-mail: [email protected]

Abstract 

We report 3 patients with MUC of the upper urinary tract who were evaluated and treated at our center between 2009 and 2011. A comprehensive Pubmed search of all case reports and literature related to MUC of the upper urinary tract was performed. In all cases, the tumors were located in the renal pelvis. All 3 patients were treated surgically. After a median follow-up of 12 months, median overall survival was 12 months. One patient presented with stage II, one with stage III and one with stage IV disease. The patient with stage II  disease is alive, with limited follow up showing no evidence of disease. The patient with stage III disease developed metastasis to the cervical lymph nodes 3 months later. Radiotherapy was performed, however she died 6 months after the initial diagnosis. The patient with stage IV disease, underwent systematic chemotherapy, but developed distant metastases (including port-site metastasis) and died 12 months after initial diagnosis. After a comprehensive search in PubMed/Medline, 50 cases have been reported. Thirty cases originated in the renal pelvis, and most patients died after surgery. MUC of the upper urinary tract often presents at an advanced stage with lymphovascular invasion and distant metastasis, and is probably an underreported variant of urothelial carcinoma associated with poor prognosis. The optimal treatment strategy is yet to be defined.

Introduction 

Micropapillary urothelial carcinoma (MUC) is an aggressive variant of urothelial carcinoma with high metastatic potential. Amin et al first reported MUC of the urinary bladder in 18 cases[1].This variant demonstrated a high tendency to invade lymphovascular spaces and to metastasize to lymph nodes and other organs. They also found MUC to be associated with advanced tumor stage and, therefore, a poor prognosis. Several other studies have confirmed these observations in MUC of the urinary bladder[2-4]. Although MUC has been well studied in the urinary bladder, there have been only a few studies of this tumor in the upper urinary tract, including the renal pelvis and ureter[5-13].The analysis of 3 consecutive cases of MUC of the upper urinary tract, may add to the current literature regarding this aggressive disease entity and may help with its future management.The literature with particular emphasis on the diagnostic and therapeutic approaches is also included and discussed.

Patients and methods

Clinical Case

After obtaining approval from the institutional review board, we retrospectively searched the files of all patients with urothelial carcinoma of the upper urinary tract (including the renal pelvis and ureter) treated at our center between 2009 and 2011. Patients were considered to have micropapillary disease if the pathology report revealed any micropapillary component (MC) in their tumor. Patient medical records were analyzed for demographic characteristics, clinical stage and outcome. Radiology, pathology and surgical reports were reviewed to determine the pathological staging at the time of nephro-ureterectomy using the 1997 TNM classification for genitourinary tumors [14]. Chemotherapy regimens, radiotherapy doses and surgical modality were also recorded. Overall survival was calculated from the date of diagnosis to the date of death or the date of last follow-up.

Search Strategy and Systematic Literature Review

We performed a comprehensive search in PubMed/Medline, up to September 2011, using the terms ‘micropapillary’, ‘renal pelvis’, ‘ureter’, ‘upper urinary tract’, ‘micropapillary urothelial carcinoma’. Articles were limited to the English language. The initial search was limited to articles from 1994 to 2011 due to micropapillary urothelial carcinoma being first reported in 1994. The inclusion criterion were original articles describing the micropapillary urothelial carcinoma of the upper urinary tract, including the renal pelvis and ureter. Exclusion criteria were articles published on the micropapilary urothelial carcinoma of urinary bladder. A total of 11 articles were included in the final analysis.

Results 

Clinical Results

Characteristics of patients at initial presentation

Between 2009 and 2011, 87 patients with urothelial carcinoma of the upper urinary tract were treated at our center. Three patients had micropapillary features. In all cases, the tumor was located in the renal pelvis. Median age at diagnosis was 67 years (59 to 75 years) and male/female ratio was 2/1. Two patients had previously smoked. The presenting symptom was macroscopic hematuria in two patients, and flank pain in one. Two of these patients had macrohematuria and were in a poor general condition, while one female patient had been treated with external beam radiotherapy for cervical lymph node metastases 5 years previously. All patients had grade 3 urothelial carcinoma and one had an associated in situ carcinoma. Lymphovascular invasion was present in all three cases (Fig.1-2.).

Figure 1. 

Figure 2. 

Metastases to regional lymph nodes were documented in two patients at the time of surgery, and to the ipsilateral adrenal gland in one patient. One patient presented with stage II, one with stage III and one with stage IV disease. The clinical characteristics of the patients are summarized in [Table 1].

Table 1. Summary of Clinical Characteristics

Case No. Age Sex Location Stage  Management Follow up
1 59 Male Renal pelvis T2 ONU* alive, no evidence ofdisease
2 67 Female Renal pelvis T3 LNU**+R^ 6 mo, died of metastasis tocervical lymph node
3 75 Male Renal pelvis T4 LNU+C# 12 mo,died of metastases tothe lung and liver.Port-stie metastasis was presented

*ONU,Open Nephro-Ureterectomy;**LNU,Laparoscopic Nephro-Ureterectomy; ^R,Radiotherapy; #C,Chemotherapy

Treatment and outcome 

One patient received open nephroureterectomy (ONU). He was alive, with limited (18months) follow up, and  showed no evidence of disease. One patient had only regional lymph node metastases, she underwent laparoscopic nephroureterectomy (LNU) and regional lymph node dissection. Her disease metastasised to her cervical lymph nodes 3 months later. Radiotherapy was performed, however she died 6 months later. One patient’s disease metastasised to the ipsilateral adrenal gland, he received LNU and excision of the affected adrenal gland. Although systemic chemotherapy was administered with gemcitabine 1000 mg/m 2 on days 1, 8 and 15,and cisplatin 70 mg/m2 on day 1 in a 28-day cycle, the disease still progressed and the patient died of metastases to his lungs and liver 12 months after surgery.

Metastatic sites

Metastases to regional lymph nodes were documented in 2 patients at the time of surgery; to the ipsilateral adrenal gland in one patient. Two out of the three patients developed distant metastases during follow up. The most frequent solid metastatic site was the lung followed by liver. One patient who underwent LNU developed port-site metastasis.

Survival data

At a median follow up of 12 months, 2 patients have died. One year survival was 66.7% and median survival was 12 months.

Systematic Review of Published Cases

After comprehensive search in PubMed/Medline, a total of 11 articles were included in the final analysis. We performed a bibliometric analysis finding a total of 50 cases of MUC of the upper urinary tract [Table 2]

Table 2. Clinical features of MUC of the upper urinary tract in literatures

Investigator Year No.cases Age*  M/F** Site(No.)# Stage(No.) Managment(No.) Follow up(No.)
Ribé 1996 1 68 1/0 P(1) T4(1) NU^+R^^+C^^^(1) 12mo,died of gastric metastases
Oh 2000 1 79 1/0 U(1) T4(1) NU+R(1) 20mo, died of gastric and peritoneal metastases
Vang 2000 1 79 0/1 U(1) T1(1)  laser ablation therapy(1) not available
Alvarado-Cabrero 2005 1 U(1) T3(1) not available
Holmäng 2006 26 69 17/9 P(19)U(6)UP(1) T1(3)T2(1)T3(18)

T4(4)

NU(14)UR^^^^(3)No¤(3)

NU+R(4)

NU+C(2)

died of tumor(20)died of other diseas(6)survived beyond 5 years(7)
Perez-Montiel 2006 5 76 3/2 P(2)U(1)UP(2) T2(1)T3(2)T4(2) NU(5) all died 3-24mo latermetastasize to regional lymph node(2),bone(1)
Munakata 2007 1 73 0/1 P(1) T4(1) NU+C(1) 14 mo,died of metastases to the left adrenal gland and the regional lymph nodes
Guo 2009 11 64.2 9/2 P(5)U(4)UP(2) T2(2)T3(8)T4(1) NU+C(11) died of tumor(4)surviving but developed metastasis(4)alvie,no evidence of disease(3)
Cheng 2010 3 64.3 2/1 P(2)U(1) T1(1) T3(1)T4(1) NU(1)NU+C(2) 15mo,died(1)alvie,no evidence of disease(2)

*Age–Mean age; **M/F–Male/Female; #Site;U–ureter,P–renal pelvis,UP–ureter and pelvis; ^NU,Nephro-Ureterectomy; ^^R,Radiotherapy; ^^^C,Chemotherapy; ^^^^UR,Ureteral Resection; ¤No,not received surgery

Discussion 

Carcinoma with a micropapillary component was first described in 1982 as a variant of endometrial carcinoma initially designated as papillary serous carcinoma of the uterus[15]. Later, this subtype was found in thyroid[16],breast[17], and lung cancers[18]. In 1994, Amin et al first reported a series of 18 cases of a micropapillary variant of transitional cell carcinoma (TCC) and suggested that this particular pattern could be associated with a more aggressive course of the tumor than usual TCC [1] .

The incidence of this disease is reported as approximately 2.8% [9]. Most cases originated from the renal pelvis; 33 patients, (including our 3 cases);15 cases arose from the ureter [6,7,8,11], and five cases were reported to have tumor both in the ureter and the renal pelvis [6,10,12]. The overall male to female ratio was 2:1(35:17). In a study by Alvarado-Cabrero, the patient’s gender and age could not be established due to incomplete clinical information.  Clinical staging information and follow up information were not available for this patient. Mean age at diagnosis is 72.07 (range  22 to 92 years). MUC of the upper urinary tract may have similar etiological factors to that of conventional UC of the upper urinary tract. It is noteworthy that two out of three patients reported by Cheng et al are both residents of the area affected by the black foot endemic in Taiwan[13]. This area has been reported to have a high prevalence of invasive upper urinary tract tumors[19-21]

There is no specific feature that allows definite clinical diagnosis of MUC of the upper urinary tract. No specific symptoms for MUC of the upper urinary tract have been reported. Painless gross hematuria was the most common symptom. Another reported symptom was flank pain. In our study, two patients presented with hematuria, one presented with flank pain. The diagnosis of MUC is based on the presence of a secondary micropapillary bud in the stroma beneath the urothelium in microscopic studies[1]. In addition to urothelial carcinoma, a micropapillary pattern has been reported in carcinomas of the ovary, breast, lung, colon, and major salivary glands[22–27 ]. In all of these organs, the micropapillary pattern shares a distinct morphology that is characteristic of small infiltrating clusters or nests of tumor cells within lacunae. Therefore, it is important to exclude metastases with micropapillary features when making a definite diagnosis of primary tumor. Immunohistochemical stains are useful in identifying the primary tumor. Ramalingam et al reported an invasive micropapillary carcinoma of the breast metastatic to the urinary bladder[28]. The micropapillary components were morphologically identical in the breast, urinary bladder, and endometrium; however, the tumor cells from the breast, endometrium, and urinary bladder were positive for cytokeratin 7 and estrogen receptor and negative for cytokeratin 20.

Therapeutic modalities depend upon a tumour’s clinical stage. They include surgery, chemotherapy and radiotherapy. Nephroureterectomy (NU) or partial ureteric resection was curative in patients with low stage disease and in a minority of those with high stage disease. In a study by Vang et al, the patient with stage I was treated by laser ablation therapy. This case appears to be less invasive because of earlier attention and intervention, but the follow up information was incomplete, and the patient’s clinical course remains to be further defined[7]. In our study, one patient with stage II disease who received NU was alive with no evidence of disease. Extensive lymph node dissection may been curative. In a study by Holmäng, one patient with multiple MC lymph node metastases who received extensive lymph node dissection survived 78 months without evidence of recurrence[9]. In our study, one patient who received regional lymph node dissection died 6 months later. According to the study of Munakat et al, radiotherapy did not influence the course of disease[11]. Oh et al reported on a 79-year-old male patient with a mid ureteric tumor treated by nephroureterectomy. The histopathological examination showed periureteric fat invasion and lymph node metastases with a predominant MC pattern in 18 of 20 lymph nodes examined. The patient had local recurrence after one year and was treated with radiotherapy but died 8 months later of metastatic disease[6]. External beam radiotherapy also did not seem to have been of benefit in our patients. Although cisplatin, cyclophosphamide, doxorubicin, gemcitabine, methotrexate and vinblastin have been reported in various combinations, nothing was effective[29-32]. The response of MUC patients to chemotherapy seems to be poor. Cheng et al prescribed chemotherapy for one patient with metastatic lesions. However, the patients died 15 months after the diagnosis[13]. Munakata et al reported one case whose pathological stage was pT4N2M1, and who underwent surgery. Although she received chemotherapy, she died of her disease 14 months postoperatively[11]. In our study, one patient had metastases to the ipsilateral adrenal gland, he received LNU and adrenalectomy, systemic GC chemotherapy (gemcitabine and cisplatin) were given, but he relapsed after 6 months and died from metastases 12 months later. However, Holmäng et al reported one case who showed partial response to methotrexate + vinblastin + doxorubicin + cisplatin followed by gemcitabine [9]. To date, no reports have recommended any preferred chemotherapy for MUC.

The prognosis is poor since most patients with MPC of the upper urinary tract initially present with advanced disease. It demonstrated a high tendency to invade lymphovascular spaces and to metastasize to lymph nodes and other organs. In a letter to the editor of the American Journal of Surgical Pathology, Ribé describes a patient who had metastasis to the gastric mucosa and died one month later[5]. Holmang et al reported 26 cases of MUC from 18 hospitals. All patients presented with invasive disease. Twenty patients died of their disease [9]. In a study by Perez-Montiel, all patients had tumors that showed high grade histologic features, and most were in an advanced clinical stage. All patients in the study died of tumor from 3 to 24 months after the diagnosis[10]. Guo reported 11, eight and one patients presenting with stage III and stage IV disease, respectively. Four died of their tumor, of the seven surviving patients, four developed metastases to the lung, colon, or retroperitoneum[12]. In our study, two  of  three  patients presented with pT3 or pT4 tumors, and two of these patients died of their disease within one year of surgery. It is noteworthy that one of the two  patients who received LNU developed port-site metastasis. To the best of our knowledge, it is first reported case in the literature of laparoscopic port-site metastasis of MUC. Therefore, we should be careful when determining the indications for laparoscopic surgery in such patients.

In conclusion, MUC of the upper urinary tract which often presents at an advanced stage with lymphovascular invasion and distant metastasis is probably an underreported variant of urothelial carcinoma associated with poor prognosis. Clinically, MUC of the upper urinary tract is far more aggressive than conventional urothelial carcinoma of the upper urinary tract. Early diagnosis of MUC and an understanding of the  nature and biologic behaviour of this tumor have important clinical implications in treatment. Patients with MUC should be diagnosed promptly and treated aggressively. Surgery is curative in less advanced cases. However, radiotherapy and systemic chemotherapy, either alone or as part of combined therapy, appear to be ineffective. The optimal treatment strategy is yet to be defined. Meanwhile, how to diagnose this disease earlier needs to be further investigated.

References  

1.Amin MB,Ro JY,el-Sharkawy T,et al.Micropapillary variant of transitional cell carcinoma of the urinary bladder: histologic pattern resembling ovarian papillary serous carcinoma. Am J Surg Pathol.1994;18:1224-1232.

2.Johansson SL, Borghede G, Holmang S.Micropapillary bladder carcinoma: a clinicopathological study of 20 cases. J Urol. 1999;161:1798–1802.

3.Maranchie JK, Bouyounes BT, Zhang PL, et al. Clinical and pathological characteristics of micropapillary transitional cell carcinoma:a highly aggressive variant. J Urol. 2000;163:748-751.

4.Kamat AM, Dinney CP, Gee JR, et al. Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients. Cancer. 2007;110:62–67.

5.Ribé A, Solé M, Campo E,et al.Papillary transitional cell carcinoma.Am J Surg Pathol. 1996 ;20:125-6.

6.Oh YL, Kim KR.Micropapillary variant of transitional cell carcinoma of the ureter.Pathol Int.2000;50:52-6.

7.Vang R, Abrams J.A micropapillary variant of transitional cell carcinoma arising in the ureter.Arch Pathol Lab Med.2000;124:1347-8.

8.Alvarado-Cabrero I, Sierra-Santiesteban FI, Mantilla-Morales A,et al.Micropapillary carcinoma of the urothelial tract. A clinicopathologic study of 38 cases.Ann Diagn Pathol. 2005;9:1-5.

9.Holmäng S, Thomsen J, Johansson SL.Micropapillary carcinoma of the renal pelvis and ureter.J Urol. 2006;175:463-6.

10.Perez-Montiel D, Hes O, Michal M,et al.Micropapillary urothelial carcinoma of the upper urinary tract: Clinicopathologic study of five cases.Am J Clin Pathol. 2006;126:86-92.

11.Munakata S, Tahara H, Kojima K,et al.Micropapillary urothelial carcinoma of the renal pelvis: report of a case and review of the literature.Med Sci Monit.2007;13:CS47-52.

12.Guo CC, Tamboli P, Czerniak B.Micropapillary variant of urothelial carcinoma in the upper urinary tract: a clinicopathologic study of 11 cases.Arch Pathol Lab Med. 2009;133:62-6.

13.Cheng YT, Luo HL, Sung MT,et al.Micropapillary variant of urothelial carcinoma: a report of 4 cases and literature review.Chang Gung Med J. 2010;33:461-5.

14.obin LH, Wittekind Ch: TNM classification of tumours of the urinary bladder.In TNM classification of malignant tumors Edited by:Sobin LH, Wittekind Ch. New York, NY: Wiley; 1997:29-31.

15.Hendrickson M, Ross J, Eifel P, et al.: Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma.  Am J Surg Pathol 1982, 6:93-108.

16.McDougall IR, Camargo CA: Treatment of Micropapillary Carcinoma of the Thyroid: Where Do We Draw the Line?  Thyroid 2007,17:1093-1096.

17.Siriaunkgul S, Tavassoli FA: Invasive micropapillary carcinoma of the breast. Mod Pathol 1993, 6(6):660-2.

18.Maeda R, Isowa N, Onuma H,et al.Lung adenocarcinomas with micropapillary components.Gen Thorac Cardiovasc Surg. 2009;57:534-9.

  1. Chiang PH, Huang MS, Tsai CJ, Tsai EM, Huang CH,Chiang CP. Transitional cell carcinoma of the renal pelvis and ureter in Taiwan. DNA analysis by flow cytometry.Cancer 1993;71:3988-92.

20.Kang CH, Yu TJ, Hsieh HH, et al.The development of bladder tumors and contralateral upper urinary tract  tumors after primary transitional cell carcinoma of the upper urinary tract. Cancer 2003;98:1620-6.

21.Chou YH, Huang CH. Unusual clinical presentation of upper urothelial carcinoma in Taiwan. Cancer 1999;85:1342-4.

  1. Haupt B, Ro JY, Schwartz MR, et al. Colorectal adenocarcinoma with micropapillary pattern and its association with lymph node metastasis. Mod Pathol.2007;20:729–733.
  2. Siriaunkgul S, Tavassoli FA.Invasive micropapillary carcinoma of the breast. Mod Pathol. 1993;6:660–662.

24.Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol. 2002;26:358–364.

  1. Nagao T, Gaffey TA, Visscher DW, et al. Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance. Am J Surg Pathol. 2004;28:319–326.

26.Burks RT, Sherman ME, Kurman RJ. Micropapillary serous carcinoma of the ovary: a distinctive low-grade carcinoma related to serous borderline tumors.Am J Surg Pathol. 1996;20:1319–1330.

27.Kim MJ, Hong SM, Jang SJ, et al. Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma. Hum Pathol. 2006;37:809–815.

28.Ramalingam P, Middleton LP, Tamboli P,et al.Invasive micropapillary carcinoma of the breast metastatic to the urinary bladder and endometrium: diagnostic pitfalls and review of the literature of tumors with micropapillary features.Ann Diagn Pathol.2003;7:112-9.

29.Regalado JJ: Mixed micropapillary and trophoblastic carcinoma of bladder: report of a first case with new immunohistochemical evidence of urothelial origin. Hum Pathol, 2004; 35: 382–84

30.Sugino Y, Negoro H, Iwamura H et al: Micropapillary variant of transitional cell carcinoma of the bladder. Int J Urol. 2004 Sep;11(9):792-4.

31.Nishizawa K, Kobayashi T, Mitsumori K et al: Micropapillary bladder cancer. Int J Urol, 2005; 12: 506–8

  1. Dhouib RS, Abbes I, Mrad K et al: Micropapillary transitional cell carcinoma of the urinary bladder. Report of two cases. Pathologica, 2005; 97: 338–40

 

Date added to bjui.org: 25/02/2012
DOI: 10.1002/BJUIw-2011-121-web

 

Radiotherapy for Leukaemic infiltration of Prostate

We present an 81 year old gentleman with haematuria and LUTS who had TURP for his outflow symptoms. Radiotherapy is an excellent option for local symptom control as evidenced in this patient.

 

Authors: Venugopal S, Das.S,  Hamid BN, Doyle.G, Leggat H, Powell CS. Countess of Chester Hospital NHS Foundation Trust
 
Corresponding Author: Suresh Venugopal, Countess of Chester Hospital NHS Foundation Trust Email: [email protected]

Abstract
Haemopoietic malignant infiltration of the prostate is unusual. When present, it brings about the dilemma on the best approach to manage it. Usually, chronic lymphocytic leukaemia is an indolent process that waxes and wanes in its course and when present with lymphadenopathy and clinical symptoms would warrant treatment with chemotherapy. When organ confined, it has a more favourable course and would be amenable to local treatments.
We present an 81 year old gentleman with haematuria and LUTS who had TURP for his outflow symptoms. The histology had confirmed a malignant lymphocytic infiltration of the prostate and he had elevated lymphocytic count and peripheral blood marker study confirming chronic lymphocytic leukaemia. He was treated with radiotherapy of his prostate. His presenting WBC count was 19.2 and PSA was 4.41 and presently his white count is 10.3 and PSA is 1.77.  He was treated with 24 Gray external beam radiotherapy to the prostate.
As we encounter an aging population, we will be seeing more of these cancers with higher incidence in the elderly. Radiotherapy is an excellent option for local symptom control as evidenced in this patient.

 

Case Report
 
Presentation
 
An 81 year old gentleman had simultaneous referral to the haematologist for low haemoglobin and raised white count and the urologist for visible haematuria and LUTS. A digital rectal examination revealed a smooth, benign-feeling prostate with a normal age-specific PSA. A CT scan done to evaluate his haematuria had picked up a large mass in the pelvis. It was difficult to differentiate whether it was of bladder or prostate origin (Figure-1).

 

Figure 1: CT scan showing pre treatment pelvic mass (left) and post treatment pelvic mass (right).

 

Trans-urethral resection of the mass showed diffuse infiltration of the prostate gland by a malignant B-cell type lymphoid infiltrate. His peripheral blood markers for chronic lymphocytic leukaemia were positive. He did not have generalised lymphadenopathy, splenomegaly or B type symptoms of leukaemia.

 

Pathology
 
The trans-urethral resection chippings of prostate showed large foci of basal cell hyperplasia and extensive infiltration with monotonous population of small lymphoid cells (Figure-2).

 

Figure 2: Prostate tissue infiltrated by lymphocytes staining strongly for CD20 (left) and H&E staining showing sheets of monotonous lymphocytic infiltration of prostate (right). 

The abnormal lymphoid infiltrate stained positively for CD5, CD20, CD79a but was negative for CD3, CD10, BCL2 and BCL6. This is keeping in with a picture of Chronic Lymphocytic Leukaemia of Prostate. There was no evidence of high grade PIN or adenocarcinoma of prostate.

 

Radiotherapy
 
In view of his symptomatic haematuria and potential for the lesion to cause local symptoms of persistence of haematuria and possible obstruction of adjacent structures, he was considered for radiotherapy after due discussion at the multidisciplinary team meeting. The pros and cons of the treatment was discussed with the patient and he opted to have the treatment. He received standard 24 Gray in 12 fractions for low grade lymphoma of the prostate (1).

 

Follow-up
 
He has since been regularly followed up at the urology clinic for his lower urinary tract symptoms with a flow rate and rectal examination on the six monthly visits as well as a yearly PSA test. He does not have any lower urinary tract symptoms. His six monthly follow-up in the haematology clinic for his Chronic Lymphocytic Leukaemia involves assessing the presence or absence of B symptoms of leukaemia as well as a peripheral blood smear assessment. At the end of three years a re-biopsy of the prostate revealed the presence of a residual malignant lymphomoid infiltrate (Figure 3).

 

Figure3: Core biopsy specimen showing lymphocytes staining strongly for CD 20 (left) and H&E staining showing monotonous lymphocytic infiltration of the core biopsy specimen of prostate (right).

 

A rescan showed the persistence of the pelvic mass but without increase in size and without any accompanying symptomatic haematuria or obstructive features.

 

Discussion
Infiltration of prostate by Chronic Lymphocytic Leukaemia is not an uncommon finding in patients with CLL. Autopsy studies have revealed CLL as the commonest secondary tumour of the prostate. Leukemic infiltration is symptomatic in only 1% of them (2). They usually present with outflow obstructive features. Chronic lymphocytic leukaemia has an indolent course with waxing and waning of the white cell count. As a haemopoietic malignancy involving the prostate, it cannot be cured by local therapies, though this has been claimed on short term follow-up in literature (3,4,5).
The prostatic component of the disease is best dealt with by radiotherapy if local problems are anticipated. Chemotherapy is reserved for patients who have systemic disease progression. Outflow obstruction is best relieved by Trans-urethral resection of the prostate. Though various doses have been cited for curative treatment of this disease, this claim is to be disputed. We currently recommend a dose of 24 Gray in 12 fractions for palliative control of symptoms as per the recommendation for a low-grade non Hodgkin’s lymphoma.
Urological follow-up of these patients is as that of other patients with outflow symptoms, who generally get a flow rate and rectal examination assessment. In addition they need to have continuous follow-up at a haematology clinic for monitoring their systemic symptoms, which may dictate the need for further intervention.
 

Lesson learnt:
• Leukaemic infiltration is not uncommon.
• It usually presents as bladder outflow obstruction requiring TURP.
• Radiotherapy is indicated only if local complications are anticipated and is not always curative.

 

References
1) https://www.rcr.ac.uk/docs/oncology/pdf/DoseFract_49_Lymphoma.pdf
2) E. H. Eddes et al, Urinary symptoms due to leukemic infiltration of the prostate A case report, Ann Haematol 1993, 66:323 – 324.
3) Mitch Jr et al, Leukemic infiltration of the prostate: A reversible form of urinary obstruction, Cancer 1970, 26: 1361-1365.
4) Belis JA, Lizza EF, Kim JC, Raich PC, Acute leukemic infiltration of the prostate. Successful treatment with radiation, Cancer 1983, 51: 2164–2167.
5) Belhiba H et al, Prostatic involvement in leukemia. Report of a case Progrès en Urologie 1992, Aug-Sep;2(4):650-2.

 

Date added to bjui.org: 15/12/2010


DOI: 10.1002/BJUIw-2010-063-web

 

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