Severe Complications in Testicular Germ Cell Tumors: The Choriocarcinoma Syndrome

Abstract

Testicular germ cell tumors (TGCTs) represent the most common solid tumor in young men and is a model of curable cancer. The effectiveness of cisplatin-based chemotherapy secures more than 95% of patients' 5-years survival rate. However, some high-risk patients with a very advanced disease develop choriocarcinoma syndrome (CS) connected with acute respiratory failure with poor prognosis and high mortality rate shortly after beginning systemic chemotherapy. CS was first described as a syndrome with hemorrhage from metastatic sites in patients with TGCTs with significantly high choriogonadotropin level. Acute hemorrhage to lung metastases is typical, but hemorrhage can occur from any metastatic site. Patognomic of choriocarcinoma cells is an invasion of small blood vessels within CS. The incidence of CS in patients with TGCTs are not well-defined and can vary across the world. To date, there are a few case reports and small retrospective series reporting a connection between systemic chemotherapy and the development of CS in metastatic TGCTs. CS is known to be triggered by massive tumor cell lysis as a result of chemotherapy and cytokine release, aggravated with alveolar hemorrhage. This can lead to a consecutive superinfection, furthered with neutropenia after chemotherapy, acute respiratory distress syndrome, rising to systemic inflammatory response, resulting in multiorgan failure and death. A reasonably effective approach in patients with extensive disease could be a shortened course of chemotherapy as well as a reduction of dosage in induction chemotherapy before full-dose chemotherapeutical regimen; however, current data regarding optimal treatment approach are limited. Patients' referral to tertiary centers and the administration of induction chemotherapy in an intensive care unit setting could further improve the treatment outcome.

Circulating microRNAs as biomarkers to assist the management of the malignant germ-cell-tumour subtype choriocarcinoma

“…As exemplified here, our identified panel of C19MC miRNAs, plus miR-517a-3p [30] and along with miR-371a-3p, offer potential advantages for monitoring patients with CHC, due to limitations of the accompanying elevated serum HCG levels, as well as for patients with embryonal carcinoma [30] , who may be AFP/HCG marker negative. Future use of serum miRNA markers to optimise management for malignant-GCT patients [15] , including those with PMNSGCTs [14] and/or pure CHC [9] , will likely improve patient outcomes. Importantly, serum miRNAs are moving from research promise towards clinical reality for the management of patients with malignant-GCTs [15] .…”

“…Issues include delayed diagnosis, with GCT not considered in a timely fashion, and thus AFP/HCG levels only requested after pathological confirmation [8] . In addition, there is a high risk of sudden respiratory decompensation [9] and/or catastrophic pulmonary [10 , 11] or cerebral [12 , 13] haemorrhage in such patients on initial instigation of treatment, known as ‘choriocarcinoma syndrome’ [9] . In such patients, close assessment in a tertiary centre intensive care setting is warranted [9] .…”

“…In addition, there is a high risk of sudden respiratory decompensation [9] and/or catastrophic pulmonary [10 , 11] or cerebral [12 , 13] haemorrhage in such patients on initial instigation of treatment, known as ‘choriocarcinoma syndrome’ [9] . In such patients, close assessment in a tertiary centre intensive care setting is warranted [9] . Furthermore, following induction chemotherapy, primary mediastinal surgery is important in patients with PMNSGCT in order to guide subsequent management [14] .…”

“…However, the long half-lives of AFP/HCG make assessment of when to perform such surgery difficult [14] . Optimising management and timing of these interventions may well improve outcomes for PMNSGCT patients [14] , including those with CHC [9] .…”

Extracorporeal Membrane Oxygenation Support as a Bridge to Recovery during Chemotherapy in a Young Patient with Metastatic Choriocarcinoma and Severe Acute Respiratory Distress Syndrome

“…Choriocarcinoma syndrome is a rare but life-threatening condition in patients with testicular germ cell tumors with widespread lung metastases, choriocarcinoma histology, and a high beta-hCG level [24]. Hemorrhage due to lung metastases is typical but may occur at any metastatic site and is often observed when beta-hCG levels are > 50,000 mIU/mL [23][24][25]. Typically choriocarcinoma syndrome occurs shortly after the administration of chemotherapy and is associated with a high mortality rate at an early phase of treatment induction [26].…”