Penile metastasis from primary cholangiocarcinoma: the first case report
- Antonio Luigi Pastore1Email author,
- Giovanni Palleschi1,
- Giorgia Manfredonia2,
- Piero Maceroni2,
- Domenico Alvaro3,
- Domenico De Santis2,
- Simone Ferretti2,
- Natale Porta4,
- Claudio Di Cristofano4,
- Carlo Della Rocca4,
- Andrea Fuschi1,
- Yazan Al Salhi1,
- Cristina Maggioni1,
- Davide Moschese1,
- Vincenzo Petrozza4 and
- Antonio Carbone1
© Pastore et al.; licensee BioMed Central Ltd. 2013
Received: 2 May 2013
Accepted: 5 October 2013
Published: 14 October 2013
Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has not been previously reported in the literature. Common metastatic sites for CCA include the regional lymph nodes and adjacent organs. CCAs are not highly vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Median survival for patients with metastatic disease is generally less than 1 year.
A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously. A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring the same histological and immunophenotypical features as the primary hepatic lesion.
To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, this article represents the first case report of penile metastasis from CCA.
KeywordsCholangiocarcinoma Elastography Magnetic resonance Penile metastases
Cholangiocarcinoma (CCA) is an uncommon and aggressive malignancy that originates in the bile duct epithelium and is associated with very poor prognosis . The incidence and risk factors of CCA vary in different regions of the world. The highest incidence is reported in the north-eastern part of Thailand. The major risk factor for CCA in this area is Opisthorchis viverrini infection, whereas Clonorchis sinensis is associated with CCA in Korea and China . Other risk factors for CCA are primary sclerosing cholangitis; biliary-duct cysts; hepatolithiasis; and conditions such as hepatitis B infection, hepatitis C infection, obesity, chronic non-alcoholic liver disease, and cirrhosis . The incidence of CCA peaks during the sixth decade of life and shows a slight male predominance. Tumours most frequently occur at the confluence of the hepatic ducts and are classified as hilar CCAs or Klatskin tumours.
The most common physical indications of CCA include symptoms such as jaundice, dyspepsia, and a palpable abdominal mass . Symptoms of CCA depend on whether the tumour mass is located in the intrahepatic area, hilar area, or extrahepatic area. Surgical intervention plays a major role in the treatment of early stage CCA and yields promising results. Patients with unresectable tumours can be treated with palliative procedures such as biliary-enteric bypass or endoscopic or percutaneous stent placement. Palliative surgical bypass is associated with a slightly improved survival rate compared to percutaneous transhepatic biliary drainage. Palliative chemotherapy does not show significant benefits, as survival rates remain low .
Common metastatic sites of CCA include the regional lymph nodes and adjacent organs. Distant metastases from CCA are uncommon, but when they do occur, they usually develop in the bone, muscle, brain, and thyroid gland [5–7]. To our knowledge, no other cases of penile metastasis from CCA have been described in the literature. Here, we report the case of a patient who presented with penile metastatic CCA and who was treated in our institution. We aim to provide useful information on this extremely rare condition.
A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously, when he underwent right posterior hepatic subsegmentectomy with lymph node dissection. No portal vein invasion had been reported, and all lymph nodes had been negative. The patient had not received adjuvant therapy after surgery. Follow-up examinations had been performed every 3 months for 2 years post-operatively and every 6 months thereafter. The patient had undergone clinical examination, laboratory tests including measurement of tumour markers, abdominal ultrasonography, and radiological investigations including chest and abdominal computed tomography. Twenty-nine months after the primary surgery, follow-up positron emission tomography-computed tomography had not revealed any elevation in the standardised uptake value at any site.
CCAs form a heterogeneous group of tumours that develop along the biliary tract, arising from different topographic regions of the biliary tree. Depending on their site of origin, they have different features and require different specific treatments. The occurrence of most CCAs is sporadic. Patients with CCA often present with non-specific symptoms such as cachexia, abdominal pain, night sweats, and fatigue. Blood tests that can be used to diagnose CCA are available. CEA and CA19-9 serum levels are often elevated in these patients, but these measurements are not sufficiently sensitive or specific to be used as a general screening tool. However, they may be useful in conjunction with imaging methods, in order to support the diagnosis of a suspected CCA. The common metastatic sites for CCA are the regional lymph nodes (hilar, peripancreatic, and periaortic lymph nodes) and adjacent organs. CCAs are not highly vascularised tumours, making haematogenous metastases uncommon. Haematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Patients with a history of CCA may also develop metastatic disease several years after first presentation. For this reason, the onset of new symptoms or signs requires adequate investigation in these patients, and a possible metastatic occurrence should be considered in order to treat it. In cases of diagnostic doubt, biopsy and histopathology combined with immunophenotypical tests should lead to an accurate diagnosis and prognosis for the patient.
Penile metastasis is always a rare event. Common primary sites are the genitourinary tract (mainly, bladder urothelial cancer and prostate adenocarcinoma) and the lower gastrointestinal tract (especially, rectum and sigmoid colon). Most cases of penile metastasis are metachronous (i.e. prostate, urothelial cancers, etc.).
The most common observed symptoms and signs of metastasis to the penis in order of frequency are priapism (up to 40%, resulting from emboli or thrombosis of dorsal vein, defined as “malignant priapism”), urinary retention, penile nodules, ulcer formation, perineal pain (7–10%), oedema, generalised swelling, broad infiltrative enlargement, dysuria, and haematuria (less than 10%).
The diagnosis in our patient was achieved by ultrasound and MRI that showed the presence of a solid lesion, which was localised in the corpora cavernosa without any involvement of the tunica albuginea and with extensive calcification of the intercavernous and intercavernospongious septa. Moreover, in our case, there were no clinical suspicious or laboratory data (PSA levels, hematuria, etc.), suggestive for malignancies that most frequently metastasize to the penis, such as prostate cancer and urothelial carcinoma.
Several mechanisms by which a tumour can secondarily affect the penis have been described; apart from the retrograde lymphatic route of spread, venous retrograde spread is the most common route, owing to the generous communication between the pelvic venous plexuses and the penile dorsal venous system [7§-9§]. Direct tumour extension has also to be considered a possible mechanism of tumour involvement.
The penile metastasis diagnosis must be established on biopsy, as was performed in this case. To differentiate metastatic lesions from primary penile tumours, an adequate specimen is needed as early as possible. It is important, though, to differentiate primary penile carcinoma from secondary metastatic disease since primary tumours are curable in a high percentage of cases.
The time interval between primary tumour and penile metastasis ranges from 3 months to 5 years and the time interval between diagnosis of penile metastasis and death ranges from 0.25 to 18 months. In our patient, metastasis became evident 3 years after the diagnosis of intrahepatic CCA. Because penile involvement by a secondary tumour usually indicates systemic dissemination, the prognosis is poor. In previously reported series, most of the patients died between 6 months and 1 year after the detection of the penile metastasis . All treatments may be considered palliative, as published clinical cases report improvement of patient symptoms without any important prolongation in survival. Prolonged survival is often possible only when a distal penile lesion or nodule is resectable; limited surgical excision or radiotherapy is usually the most useful modality. Partial or total penectomy will be required with highly invasive neoplasms involving the corporal bodies.
To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, to our knowledge this article represents the first case report of penile metastasis from CCA.
Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Epithelial membrane antigen
Magnetic resonance imaging.
The authors declare that the manuscript has not been supported by any sources of support, including sponsorship and any sources of material.
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