Abstract
Arab Journal of Urology (2013) 11,48–53 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com ONCOLOGY/RECONSTRUCTION Unusual presentations of prostate cancer: A review and case reports Ahmed Elabbady, Ahmed Fouad Kotb Department of Urology, Alexandria University, Alexandria, Egypt Received 15 September 2012, Received in revised form 29 October 2012, Accepted 29 October 2012 Available online 6 December 2012 KEYWORDS Abstract Objective: To report our institutional experience with some rare presen- tations of prostate cancer, as prostate cancer is a common problem and affects a Prostate cancer; large group of men during their lifetime, but a few studies report unusual presenta- Supraclavicular lymph tions of metastatic prostate cancer. node; Methods: All possible clinical and pathological data were collected for six rele- Hydronephrosis; vant patients with prostate cancer and unusual metastases who were identified at Constipation our institution. PubMed was searched for unusual presentations of prostate cancer in the last 20 years (1982–2012) and all relevant publications were assessed. The authors discussed the reports and selected those articles of major clinical significance to include in a review. Results: We identified 19 reports of major clinical significance and reviewed them. As in the cases from our institution, supraclavicular lymphadenopathy, isolated upper ureteric obstruction and severe obstructing constipation were some of the rare presentations encountered at other institutions, and reported mostly as sporadic case-reports. Conclusion: Prostate cancer should be always considered in the differential diag- nosis of elderly men presenting with supraclavicular lymphadenopathy, hydrourete- ronephrosis or constipation, even in the presence of a normal digital rectal examination and low serum total prostate-specific antigen (PSA) levels. PSA immu- nohistochemical staining should be used in doubtful cases. ª 2012 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. Corresponding author. Tel.: +20 1203021316. E-mail address: drahmedfali@gmail.com (A.F. Kotb). Introduction Peer review under responsibility of Arab Association of Urology. Prostate cancer is a common problem that in most cases starts to develop at the age of 50 years and reaches its Production and hosting by Elsevier peak incidence at 60–70 years of age. The prognosis of 2090-598X ª 2012 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.aju.2012.10.002 Unusual presentations of prostate cancer: A review and case reports 49 prostate cancer mainly depends on the presence or hard, irregular prostate, and clinical T3 disease, with a absence of metastatic spread [1]. Prostate cancer usually serum PSA level of 180 ng/mL. CT of the abdomen metastasises to the bony skeleton, followed by lungs, and a bone scan showed no abnormality, with no skele- liver, pleura and adrenal glands [2]. Rarely prostate tal metastases and no abdominal lymphadenopathy. A cancer can present with non-regional lymph nodes or limited TURP and TRUS-guided prostatic biopsies de- soft-tissue metastases, and such presentations are usu- tected prostate cancer of Gleason 4 + 5 in all six cores ally communicated as sporadic case-reports. taken. Bicalutamide 50 mg/day was started, followed The aim of the present study was to review previous by an LHRH agonist, resulting in a good PSA response reports of unusual metastatic presentations of prostate (reduced to 0.09 ng/mL). After 1 year of controlled dis- cancer, and to report our experience with such cases. ease the patient was followed while on intermittent androgen blockade. During the off-treatment period Methods the patient presented with a large, hard and fixed left supraclavicular lymph node, with a PSA level of 12 All relevant clinical and pathological data were collected ng/mL and no abnormality on CT of the abdomen or for six relevant patients identified at our institution. pelvis. The patient refused to have a biopsy from a neck Medline was searched, using PubMed, for reports pub- mass. We restarted total androgen blockade, resulting in lished in the last 20 years (1982–2012), focusing on unu- a good PSA response and complete resolution of the sual presentations of prostate cancer and using the supraclavicular mass within 3 months. After another keywords ‘prostate cancer’, ‘supraclavicular lymph year of complete androgen blockade the patient chose node’, ‘hydronephrosis’, and ‘constipation’. All relevant to take the drug intermittently and he has been followed publications were collected and the authors discussed up to the present, with no evidence of progression of the choosing the articles of major clinical influences to in- supraclavicular mass. clude in our review. The third case was a 76-year-old man who presented with a high PSA level (123 ng/mL) and locally advanced Results prostate cancer, classified as T3N2M0 disease. The TRUS-guided biopsy showed Gleason 4 + 3 in all four From our practice we identified several unusual presen- cores taken. The patient was treated with continuous to- tations of metastatic prostate cancer. tal androgen blockade and conformal radiotherapy. However, 3 years later castration resistance started to Supraclavicular lymph node emerge, and a right-sided hard supraclavicular mass ap- peared. We tried anti-androgen withdrawal, added keto- The first case was a 57-year-old man who presented with conazole and corticosteroids, and there was a partial a right hard supraclavicular mass, 2 cm in diameter, that biochemical and clinical response for a few months. was followed 2 months later by aphasia and right-sided After 6 months the patient was referred to medical hemi-paresis. During the 2-month period, the supracla- oncology, and chemotherapy was started, allowing par- vicular mass doubled in size. CT showed brain tumours tial remission of the supraclavicular lymph node. affecting the left temporal, parietal and frontal lobes, that were suspected to be metastases. The patient had Ureteric adventitia no urinary complaints, a DRE detected a hard irregular prostate (clinically T3), and the serum PSA level was 151 ng/mL. CT showed no abdominal or pelvic lym- A 62-year-old man presented with left loin pain that had phadenopathy, but only diffuse skeletal metastases. We started a few months previously. Ultrasonography immediately started the patient on bicalutamide 150 mg showed left-sided grade 3 hydroureteronephrosis, and daily with corticosteroids. Limited TRUS-guided pros- IVU confirmed a provisional diagnosis of PUJ obstruc- tion. (Fig. 1). The patient had no LUTS and a DRE tatic biopsies confirmed the diagnosis of prostate cancer, Gleason 4 + 5 in all four cores that were taken. On the showed a hard irregular prostate, and the serum total third day of treatment the patient had marked improve- PSA level was 142 ng/mL. Multi-slice CT showed a left ments in speech and in limb weakness. LHRH analogues peri-ureteric mass, enlarged left iliac and para-aortic were added to the treatment regimen. The supraclavicu- lymph nodes, together with multiple lytic lesions in the lar mass regressed in size by 80% after 2 weeks and vertebral spines. Fig. 2 shows the findings from CT. disappeared completely after 8 weeks. The patient was TRUS-guided prostatic biopsies confirmed the diagnosis followed up for >18 months, on intermittent androgen of prostate cancer, Gleason 4 + 3. Bicalutamide blockade, and showing stable disease. 150 mg/day was started, followed later by injections The second case was a 77-year-old man who pre- with an LHRH analogue. At 2 weeks after the first dose sented to the urology clinic with acute urinary retention of LHRH analogue IVU showed a marked improve- and a history of TURP, undertaken 4 years previously, ment of the PUJ obstruction and the pain was resolved with a pathology report of BPH. The DRE revealed a (Fig. 3). 50 Elabbady, Kotb Figure 3 The follow-up IVU, after hormonal treatment, show- ing an improvement in the obstruction. Figure 1 Initial IVU showing the left PUJ obstruction. TRUS confirmed the diagnosis of prostate cancer, Glea- son 3 + 4. A bone scan showed metastatic deposits. Immediate complete androgen blockade for 6 months resulted in a marked improvement in the patient’s symp- toms. The other patient presented to a general surgeon, who diagnosed advanced rectal carcinoma. The patient was wrongly managed with a colostomy, but he had no relief and presented to another general surgeon who, after examination, referred the patient for urolog- ical consultation. When examined the prostate was hard and hugely enlarged, with T4 disease. The PSA level was then 121 ng/mL, and TRUS biopsies confirmed a tu- mour of Gleason score 4 + 3. A bone scan showed deposits. Bilateral orchidectomy resulted in a marked improvement and the colostomy was closed. Previous reports We identified 19 publications of major clinical signifi- cance and included them in our review. As in the patients from our institution, they included supraclavicular lym- phadenopathy, but also isolated upper ureteric obstruc- Figure 2 CT of the abdomen and pelvis, showing an extensive tion and severe obstructing constipation as rare left peri-ureteric mass. presentations encountered in different institutions, and communicated in most cases as sporadic case-reports. Supraclavicular lymphadenopathy secondary to pros- Constipation tate cancer was the most discussed unusual presentation and we identified 16 reports of clinical significance. Most We had two patients (70 and 62 years old) who both ini- reports discussed possible dissemination to the left tially presented with severe constipation. MRI in the supraclavicular lymph nodes. One report described an first patient showed a huge mass bulging into the rec- isolated right supraclavicular nodal dissemination from tum. The serum PSA level was 480 ng/mL and limited prostate cancer. Of the three patients we identified with Unusual presentations of prostate cancer: A review and case reports 51 prostate cancer one presented with right supraclavicular of left-sided metastases. They also found that the serum lymphadenopathy. PSA level was not elevated in half of the patients pre- Soft-tissue metastases to the ureteric adventitia were senting with supraclavicular nodal metastasis, confirm- of interest and we found two case reports of major clin- ing the need for specific tissue staining. Wang et al. ical significance, as these cases were wrongly managed [12] reported three cases of metastatic prostate cancer by nephroureterectomy. We found one case of upper initially presenting with a left supraclavicular mass. ureteric adventitial spread from prostate cancer that One of them had an associated right supraclavicular was diagnosed before surgical intervention and pro- mass. CT of the abdomen confirmed associated general- gressed well on hormonal treatment. ised lymphadenopathy. Ahn et al. [13] reported a case of A third interesting unusual presentation of prostate prostate cancer in a 34-year-old man that initially pre- cancer was severe constipation, not responding to regu- sented with a diagnosis resembling lymphoma. This pa- lar medications. We identified one report and describe tient had bilateral supraclavicular and inguinal two cases from our practice. lymphadenopathy, associated with mediastinal, abdom- inal and pelvic lymphadenopathy. The patient had no Discussion urinary symptoms, a normal DRE, but a markedly ele- vated serum PSA level. The diagnosis was then con- Lymph nodes are commonly involved during the course firmed by PSA immunohistochemical staining. There of metastatic prostate cancer, with hypogastric and was a marked improvement in the patient’s condition obturator lymph nodes as the most common sites [3]. after a bilateral orchidectomy. Further spread can occur to the para-aortic nodes, to Tsujino et al. [14] reported a case of prostatic cisterna chili, to the thoracic duct, and then to the left adenocarcinoma presenting with supraclavicular and subclavian vein, and to the systemic circulation [4]. Tu- mediastinal lymphadenopathy, with CT and fluorode- mour cells can theoretically lodge in the left supraclavic- oxyglucose-positron emission tomography confirming ular lymph nodes in a retrograde fashion. Batson [5] no abnormalities in the prostate or pelvic lymph nodes. suggested that the supradiaphragmatic extension of Their patient had no urinary symptoms. The patient prostate cancer occurs haematogenously via the verte- had a good response after hormonal therapy. These bral venous system, or Batson’s plexus, accessible via di- authors raised concern about the possibility of misdiag- rect extension from the primary prostate cancer. nosing metastatic prostate cancer to supradiaphragmatic Supraclavicular lymph nodes are commonly affected lymph nodes as lung cancer, with inappropriate treat- during the course of metastasis of the lungs, head, neck, ment by chemotherapy. salivary glands and thyroid cancer [6]. Distant primaries Cho et al. [15] studied 26 cases of prostate cancer met- rarely involving supraclavicular nodes include those in astatic to supradiaphragmatic lymph nodes, including 15 the kidney and the breast [6]. The incidence of involve- with left supraclavicular lymph node involvement. They ment secondary to prostate cancer has been reported to showed that nearly half of the cases had normal DRE be <0.4% as a part of widespread metastatic disease [7,8]. findings and a normal serum PSA level. They concluded Few studies have indicated the possibility of supracla- that metastatic prostate cancer should be excluded in vicular lymph node involvement during the course of men aged >45 years, even if there was no high serum prostate cancer metastasis. Nearly all available publica- PSA level and normal DRE findings. Few other authors tions reported an association of prostate cancer with the reported sporadic case-reports of prostate cancer metas- left supraclavicular lymph node, as a single metastasis or tasising to the supraclavicular lymph nodes [16–18]; as a part of generalised lymphadenopathy. Table 1 lists the previous publications. Saeter et al. [9] studied 47 patients with carcinoma of The present study is the second to report the right the prostate, who at the time of diagnosis had soft tissue supraclavicular lymph node to be the single non- or non-regional lymph nodes involved. They reported regional gross metastasis of prostate cancer, despite that the left supraclavicular fossa was the most common site of extra-skeletal non-regional lymphatic spread, and Table 1 Studies describing supraclavicular lymphadenopathy, the survival of such cases was similar to those presenting as rare metastases from prostate cancer. with skeletal metastases, and with an equal response to Study Regional lymphadenopathy Laterality L/R N cases hormonal therapy. Platania et al. [10] reported a case [10] No 1/0 1 of prostate cancer presenting with enlarged left supra- [12] Yes 3/1 3 clavicular lymph nodes. Biopsy showed an undifferenti- [13] Yes 1/1 1 ated adenocarcinoma of unknown origin. PSA staining [14] No 1/0 1 [15] No 15/0 15 confirmed the diagnosis of prostate cancer. [16] Yes 1/0 1 Jones and Anthony [11] detected 11 patients with [17] No 0/1 1 metastatic prostate cancer during a survey of 250 cervi- [18] No 1/0 1 cal lymph nodal biopsies from men. These cases repre- Present Yes 1/2 3 sent 11% of all cases metastatic to the neck, and 20% 52 Elabbady, Kotb the absence of abdominal and pelvic lymphadenopathy. personal experience and our two cases, we think that Being only associated with brain metastases this might every man presenting with constipation refractory to confirm the theory of Batson [3] of a vascular, rather treatment should be assessed for possible locally ad- than lymphatic, route of spread to the supradiaphrag- vanced prostate cancer. One of our patients was unlucky matic lymph nodes. Our first patient had a high Gleason to be managed wrongly by a diverting colostomy, and grade and large-volume prostatic tumour, but again the we understand that there might be others managed in metastases showed a good response to hormonal ther- the same way and who are still under-diagnosed. apy that persisted to the present. The second case repre- In conclusion, prostate cancer should be always con- sented recurrent disease during the off-treatment period sidered in the differential diagnosis of elderly men pre- of LHRH and bicalutamide, while the third case was senting with supraclavicular lymphadenopathy, associated with the start of castration-resistant disease. hydroureteronephrosis or constipation, even in the pres- These cases also confirm that supraclavicular lymph ence of a normal DRE and low serum total PSA level. node involvement responds to treatment in the same PSA immunohistochemical staining should be used in way as skeletal metastases. Our patients responded to doubtful cases. The DRE should not be ignored in any alternative hormonal treatment and to chemotherapy elderly man, regardless of the presenting symptoms in the same way as those with skeletal metastases. and the provisional diagnosis. Although we did not use immunohistochemical stain- ing in the present cases, due to the association with a Conflict of Interest high PSA level and a known history of metastatic pros- tate cancer in two of them, we believe that it is impor- None. tant in all cases of a supraclavicular mass in elderly men, noting that most of these patients are not initially Source of Funding seen by urologists. Ureteric adventitia as an unusual site of soft-tissue None. metastases from prostate cancer has been reported spo- References radically. Chalasani et al. [19] reported a 68-year-old man who presented with LUTS and right loin pain. [1] Bubendorf L, Scho¨ pfer A, Wagner U, Sauter G, Moch H, Willi The diagnostic evaluation, including PSA analysis, N, et al. Metastatic patterns of prostate cancer: an autopsy study TRUS-guided biopsies and cystoscopy, showed prostate of 1,589 patients. Hum Pathol 2000;31:578–83. cancer and bladder TCC. Ureteroscopy showed a suspi- [2] Mundy GR. Metastasis to bone. 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Journal
Arab Journal of Urology
– Taylor & Francis
Published: Mar 1, 2013
Keywords: Prostate cancer; Supraclavicular lymph node; Hydronephrosis; Constipation
