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1.  Choroidal metastasis as the presenting feature in a case of testicular choriocarcinoma 
Saudi Journal of Ophthalmology  2012;26(2):249-251.
A twenty-six year old male with decreased vision in right eye was diagnosed with non-rhegmatogenous retinal detachment. Further evaluation revealed a yet undiagnosed left testicular mass found to be choriocarcinoma on histopathology. Chemotherapy resulted in complete remission; however, there was no improvement in vision. There is a substantial risk of visual loss in the presence of ocular metastatic lesions. Early detection and treatment is highly effective in terms of tumor control and a more favorable survival and visual outcome. The onus of the ocular diagnosis lies on the ophthalmologist. The presence of a testicular origin tumor must be considered in a young male with intraocular metastasis.
PMCID: PMC3729854  PMID: 23961001
Choroidal metastasis; Retinal detachment; Choriocarcinoma of testis
2.  Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours 
Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell.
Case presentation
A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission.
The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma) should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation.
PMCID: PMC1697810  PMID: 17112390
3.  Retroperitoneal teratoma with somatic malignant transformation: A papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy 
BMC Urology  2013;13:9.
Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation.
Case presentation
A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.
Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer.
To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.
PMCID: PMC3577457  PMID: 23402579
Retroperitoneal teratoma; Malignant transformation; Germ cell tumour metastasis; Renal cell cancer
4.  Osteolytic bone destruction resulting from relapse of a testicular tumour 23 years after inguinal orchiectomy and adjuvant chemotherapy: a case report 
Late relapse of a testicular germ cell tumour is an uncommon occurrence. We report a case of osteolytic bone metastasis appearing 23 years after the initial treatment of a metastatic testicular mixed tumour (choriocarcinoma and embryonal carcinoma). This is one of the longest periods of recurrence reported for testicular germ cell tumours.
Case presentation
A 52-year-old Caucasian man who underwent a right inguinal orchiectomy due to testicular tumour in 1984 presented to our outpatient clinic in a generally bad condition of health and with severe pain of his right hip joint and os ischii caused by osteolytic metastasis.
This case emphasizes the need for a life-long follow-up of patients with primary metastatic testicular cancer.
PMCID: PMC2737795  PMID: 19830236
5.  Late onset of subfoveal choroidal neovascularisation following cerebral radiotherapy 
BMJ Case Reports  2010;2010:bcr0520091825.
A report of choroidal neovascularisation (CNV) associated with radiation retinopathy. A 43-year-old Caucasian man presented with a 4-week history of sudden loss of central vision in the left eye, 8.5 years following radical radiotherapy for left tempero-parietal anaplastic astrocytoma. His visual acuity was 6/6 in the right eye and 6/60 in the left eye. Ophthalmoscopy of the left eye showed central macular pigmented area surrounded by subretinal fluid, haemorrhage and exudates. Fundus fluorescein angiography revealed left subfoveal CNV with surrounding macular oedema and peripheral retinal ischaemia. Radiation retinopathy associated CNV is a late ocular complication of cerebral radiotherapy. It should be investigated as a possible aetiology of severe visual loss in long-term survivors of cerebral tumours who have previously received radiotherapy.
PMCID: PMC3027866  PMID: 22797201
6.  Intracranial choriocarcinoma occurrence in males: Two cases and a review of the literature 
Oncology Letters  2013;6(5):1329-1332.
Choriocarcinomas generally develop in females. Non-gestational choriocarcinoma in males is extremely rare. The present study describes two cases of young males who were diagnosed with intracranial choriocarcinoma. One case was of an aggressive choriocarcinoma with multiple metastases to the brain, but with an unidentified origin. The patient was admitted in the terminal stage of the cancer. Although a tumor resection was performed, the condition of the patient rapidly deteriorated and chemotherapy was not recommended. The patient succumbed nine days after the surgery. The second case was of a primary ventricular choriocarcinoma. The patient was hospitalized for acute hydrocephalus caused by a mass that was located in the ventricle. Following a tumor resection, the patient underwent a course of whole-brain and spinal radiotherapy. The patient was followed up for more than half a year and remained in a good condition. The present study describes the two cases and a comprehensive review of the literature that was performed to identify similar studies that document choriocarcinomas in males.
PMCID: PMC3813813  PMID: 24179518
intracranial choriocarcinomas; male; tumorigenesis; prognosis
7.  Testicular seminomatous mixed germ cell tumor with choriocarcinoma and teratoma with secondary somatic malignancy: a case report 
Testicular tumors are a heterogeneous group of neoplasms exhibiting diverse histopathology and can be classified as seminomatous and non-seminomatous germ cell tumor types. Mixed germ cell tumors contain more than one germ cell component and various combinations have been reported. Here, we present a rare case of a mixed germ cell tumor composed of seminoma, choriocarcinoma and teratoma with a secondary somatic malignancy.
Case presentation
A 31-year-old Caucasian man presented with splenic rupture to our hospital. A right-sided testicular swelling had been present for 6 months and his alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase were increased. An ultrasound of his scrotum revealed an enlarged right testis with heterogeneous echogenicity. Multiple hypervascular lesions were noted in his liver and spleen. He underwent transcatheter embolization therapy of his splenic artery followed by splenectomy and right-sided orchiectomy. A computed tomography scan also showed metastasis to both lungs. During his last follow up after four cycles of cisplatin-based chemotherapy, the level of tumor markers had decreased, decreases in the size of his liver and pulmonary lesions were noted but new sclerotic lesions were evident in his thoracolumbar region raising concern for bony metastasis.
Prognosis of testicular tumor depends mainly on the clinical stage, but emergence of a sarcomatous component presents a challenge in the treatment of germ cell tumors and the histological subtype of this component can be used as a guide to specific chemotherapy in these patients.
PMCID: PMC3917416  PMID: 24380446
Mixed germ cell tumors; Rhabdomyosarcoma; Sarcomatous component
8.  Choroidal metastasis from early rectal cancer: Case report and literature review 
•We report a case of choroidal metastasis from early rectal cancer.•Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases.•The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye.
Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer.
A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases.
Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression.
This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer.
PMCID: PMC4276086  PMID: 25460493
Choroidal metastasis; Colorectal cancer
9.  Intramedullary Spinal Cord Metastasis of Choriocarcinoma 
The authors describe a case of choriocarcinoma that metastasized to the cerebral cortex, vertebral body, and intramedullary spinal cord. A 21-year-old woman presented with sudden headache, vomiting and a visual field defect. Brain computed tomography and magnetic resonance examinations revealed an intracranial hemorrhage in the left temporo-parietal lobe and two enhancing nodules in the left temporal and right frontal lobe. After several days, the size of the hemorrhage increased, and a new hemorrhage was identified in the right frontal lobe. The hematoma and enhancing mass in the left temporo-parietal lobe were surgically removed. Choriocarcinoma was diagnosed after histological examination. At 6 days after the operation, her consciousness had worsened and she was in a state of stupor. The size of the hematoma in the right frontal lobe was enlarged. We performed an emergency operation to remove the hematoma and enhancing mass. Her mental status recovered slowly. Two months thereafter, she complained of paraplegia with sensory loss below the nipples. Whole spine magnetic resonance imaging revealed a well-enhancing mass in the thoracic intramedullary spinal cord and L2 vertebral body. Despite chemotherapy and radiotherapy, the patient died 13 months after the diagnosis.
PMCID: PMC3358599  PMID: 22639709
Choriocarcinoma; Intracerebral hematoma; Intramedullary spinal cord metastasis; Spinal metastasis
10.  Incidental placental choriocarcinoma in a term pregnancy: a case report 
Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario.
Case presentation
The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well.
Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.
PMCID: PMC2577684  PMID: 18922186
11.  Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture 
Eye  2012;26(9):1157-1172.
Uveal melanomas are diverse in their clinical features and behaviour. More than 90% involve the choroid, the remainder being confined to the ciliary body and iris. Most patients experience visual loss and more than a third require enucleation, in some cases because of pain. Diagnosis is based on slit-lamp biomicroscopy and/or ophthalmoscopy, with ultrasonography, autofluorescence photography, and/or biopsy in selected cases. Conservation of the eye with useful vision has improved with advances in brachytherapy, proton beam radiotherapy, endoresection, exoresection, transpupillary thermotherapy, and photodynamic therapy. Despite ocular treatment, almost 50% of patients develop metastatic disease, which occurs almost exclusively in patients whose tumour shows chromosome 3 loss and/or class 2 gene expression profile. When the tumour shows such lethal genetic changes, the survival time depends on the anatomical stage and the histological grade of malignancy. Prognostication has improved as a result of progress in multivariate analysis including all the major risk factors. Screening for metastases is more sensitive as a consequence of advances in liver scanning with magnetic resonance imaging and other methods. More patients with metastases are living longer, benefiting from therapies such as: partial hepatectomy; radiofrequency ablation; ipilumumab immunotherapy; selective internal radiotherapy; intra-hepatic chemotherapy, possibly with isolated liver perfusion; and systemic chemotherapy. There is scope for improvement in the detection of uveal melanoma so as to maximise any opportunities for conserving the eye and vision, as well as preventing metastatic spread. Patient management has been enhanced by the formation of multidisciplinary teams in specialised ocular oncology centres.
PMCID: PMC3443832  PMID: 22744385
uveal melanoma; detection; diagnosis; treatment; screening; metastatic disease
12.  Successful synchronous chemotherapy and radiotherapy followed by consecutive chemotherapy without surgery for primary intracranial choriocarcinoma: A case report 
Oncology Letters  2012;4(6):1389-1391.
We experienced a rare case of primary intracranial choriocarcinoma treated successfully with synchronous chemotherapy and radiotherapy followed by three consecutive courses of chemotherapy without surgery. A 19-year-old male patient presented with a two-week history of diplopia, headache, nausea and vomiting. Neurological examination revealed visual disturbance, bilateral hearing loss, bilateral sixth nerve palsy, left skew deviation, downgaze limitation and clockwise torsional nystagmus on the left upgaze. During image evaluation, the patient suddenly presented with a confused mental status, bradycardia and decreased respiration. An emergency third ventriculostomy was conducted, followed by synchronous ifosfamide, cisplatin and etoposide chemotherapy (ICE; I, 900 mg/m2; C, 20 mg/m2; and E, 60 mg/m2) on days 1–5, and external radiotherapy (whole brain, 30 Gy/15 Fxs; local boost, 30 Gy/15 Fxs) followed again by three consecutive courses of chemotherapy. This therapy resulted in tumor regression by 63% and full improvement in the patient’s neurological condition. However, it was difficult to remove the remaining tumor using a surgical approach due to the risk of postoperative hemorrhage and limited access. We planned to observe the remaining mass without surgery. This patient is now alive and the mass size has not changed for 18 months since treatment. This is the first report of the effectiveness of synchronous chemotherapy and radiotherapy followed by consecutive chemotherapy without surgery in a patient with primary intracranial choriocarcinoma.
PMCID: PMC3506719  PMID: 23205140
synchronous chemotherapy and radiotherapy; consecutive chemotherapies; primary intracranial choriocarcinoma
13.  Pure choriocarcinoma of the testis presenting with jaundice: a case report and review of the literature 
Testicular cancer is the most common malignancy in men 15- to 35-years-old. The North American standard classification divides testicular cancers into germ cell tumors and non-germ cell tumors. The lymphatic spread of germ cell tumors usually involves the retroperitoneal lymph nodes. However, this spread to the retroperitoneum rarely involves the hepatic hilum. We describe an unusual case of metastatic choriocarcinoma of the testis that was clinically mimicked by a cholestatic jaundice. This is an unusual presentation of testicular cancer and, to the best of our knowledge, the first report of this kind in the literature.
Case presentation
A 28-year-old Moroccan man presented with a four-week history of progressive obstructive jaundice, and weight loss to our emergency department. Abdominal ultrasound showed a dilatation of the biliary ducts due to pathologically enlarged lymph nodes of the hepatic hilum. A complete clinical and radiologic assessment to discover the primary tumor was negative except for pulmonary metastasis. In the laboratory findings at admission there were signs of cholestasis with an abnormal increase in the rate of testicular tumor markers (serum beta-human chorionic gonadotropin level was 11,000IU/ml), which subsequently led to the suspicion of a testicular tumor. Further evaluation included testicular palpation and ultrasound which revealed a testicular nodule. The patient underwent an inguinal orchidectomy of the right testis and histopathological examination confirmed a pure choriocarcinoma. The prognosis was poor due to lymph node involvement at the hepatic hilum. He died one month later, despite general chemotherapy.
The clinical presentation of the disease and the rarity of this entity are two remarkable characteristics described in this case report which are rarely reported in literature.
PMCID: PMC3469387  PMID: 22938171
Choriocarcinoma of testis; Testicular tumor; Metastasis
14.  Sequential bilateral testicular tumours presenting with intervals of 20 years and more 
BMC Urology  2013;13:71.
About 3 – 5% of all patients with testicular germ cell tumour (GCT) develop a contralateral cancer, the majority of which arise within 10–15 years. Little is known about the risk of second GCTs after more than two decades. Here we present 3 cases with very late presenting contralateral GCT and provide a summary of similar cases reported previously.
Case presentations
(1) This white Caucasian man underwent right-sided orchiectomy for a nonseminomatous GCT at the age of 22 years. Additional treatment consisted of retroperitoneal lymph node dissection (RPLND) and chemotherapy with 4 cycles of vinblastin / bleomycin. 36 years later, contralateral seminoma clinical stage 1 developed. Cure was achieved by orchiectomy. Histologically, testicular intraepithelial neoplasia (TIN; intratubular germ cell neoplasia) was detected in the tumour-surrounding tissue.
(2) This white Caucasian male had right-sided orchiectomy for nonseminomatous GCT at the age of 29 years. Pathological stage 1 was confirmed by RPLND. 25 years later, he received left sided orchiectomy for seminoma stage 1. Histologically, TIN was found in the tissue adjacent to seminoma. Two brothers had testicular GCT, too, one with bilateral GCT. (3) This 21 year old white Caucasian man underwent left-sided orchiectomy for nonseminomatous GCT. Pathological stage 1 was confirmed by RPLND. 21 years later, he received organ-preserving excision of a right-sided seminoma, followed by BEP chemotherapy for stage 3 disease. Histologically, TIN was found in the surrounding testicular tissue.
22 cases of bilateral GCT with intervals of 20 or more years have previously been reported, thereof three with intervals of more than 30 years, the longest interval being 40 years.
Apart from increased risks of cardiovascular diseases and non-testicular malignancies, patients with GCT face the specific probability of a second GCT in the long run. This risk persists life-long and is not eliminated by chemotherapy. Contralateral testicular biopsy can identify patients at risk by revealing precursor cells of GCT though false-negative biopsies may occur sporadically. However, in view of the multi-facetted late hazards of GCT patients, this minor surgical procedure might somewhat simplify the long-time care of these patients.
PMCID: PMC4028980  PMID: 24321309
Testicular germ cell neoplasms; Bilateral tumours; Testicular biopsy; Seminoma; Familial germ cell tumours
15.  Metastasectomy as optimal treatment for late relapsing solitary brain metastasis from testicular germ cell tumor: a case report 
BMC Research Notes  2014;7(1):865.
Management of late relapse of a testicular germ cell tumor is difficult because few cases have been reported and the tumors are intractable to chemotherapy. Here we present a case with a single brain metastasis from late relapse of a testicular germ cell tumor. This is the first report of a brain metastasis that was treated successfully only by surgery.
Case presentation
A 19-year-old Japanese man presented with breathing difficulties and left testis enlargement and he was diagnosed with a yolk sac tumor following a left orchiectomy. At the time of diagnosis, multiple lung metastases were apparent on computed tomography, and serum alpha-fetoprotein level was elevated to 10,245 ng/ml. The patient received three postoperative courses of bleomycin, etoposide and cisplatin and etoposide and cisplatin respectively and a complete response was obtained. Four years after surgery, the patient was admitted to the hospital due to a sudden seizure. High alpha-fetoprotein levels (539 ng/ml) were evident and magnetic resonance imaging suggested a 45-mm single brain tumor in the right parietal lobe, for which surgery was performed. The pathological diagnosis was yolk sac tumor. The alpha-fetoprotein level remained normal at 2 months after operation. There was no recurrence 24 months post-operation.
Chemoresistance and late neurotoxicity are concerns in treating brain metastasis with chemotherapy or cerebral radiotherapy. Surgery is believed to be the optimal treatment choice if the size of the brain metastasis is larger than 35-mm and the late relapse area is surgically accessible.
PMCID: PMC4265396  PMID: 25444462
Late relapse; Testicular germ cell tumor; Yolk sac tumor; Brain metastasis; Surgery
16.  Ocular metastases from HER2 positive breast carcinoma and the response to combination therapy with Paclitaxel and Trastuzumab: a case report 
Cases Journal  2009;2:9143.
Breast cancer is the most common tumour to metastasize to the uveal tract. The mean survival period after diagnosis of metastasis to the eye, ranges from 10 to 32 months. However, recent advances in therapy including the use of monoclonal antibody therapy, will hopefully improve treatment outcomes and prolong survival rates.
We report a case of a 45 year old woman with a HER2 positive breast cancer, who developed two metastatic lesions in the left choroid, and the left optic nerve sheath. She underwent treatment with a combination of chemotherapy (Paclitaxel) and anti-HER2 monoclonal antibodies (Trastuzumab).
Nine months after treatment, a B-scan showed resolution of the superior choroidal focus, as well as absence of blood flow within the optic nerve sheath. The inferonasal lesion was still present but the dimensions were reduced.
The patient underwent a combined treatment of chemotherapy and Trastuzumab to increase the response rate. Trastuzumab is a humanized monoclonal antibody, which binds to the extracellular segment of the HER2/neu receptor. Nine months following the therapy her vision was stable, whilst one focus of the tumour in the affected eye, had regressed. The favourable response highlights the significant impact of this new therapy, as an alternative to external beam radiotherapy in patients with ocular metastasis from HER2 (+) breast cancer.
PMCID: PMC2803940  PMID: 20062660
17.  Papillary Thyroid Carcinoma: Bilateral Choroidal Metastases with Extrascleral Extension 
Here, we present the case of a patient with bilateral choroidal metastases with extraocular extension in one eye. Metastasis of papillary thyroid carcinoma to the uvea is extremely rare, with only 6 patients reported in the literature. A 62-year-old man with a prior history of papillary thyroid carcinoma suffered the rapid loss of vision in his right eye. He had neovascular glaucoma, total retinal detachment, and a solitary choroidal mass. A month later, his left visual acuity also decreased because of a small macular choroidal mass. The right eye was enucleated and a nodular lesion over the sclera representing extraocular extension was observed. This tumor and the intraocular lesion were composed of papillary excrescences and cystic spaces and stained positively for thyroid transcription factor 1 and thyroglobulin, all confirming the diagnosis of metastatic papillary thyroid carcinoma. The tumor in the left eye was successfully treated with diode laser transpupillary thermotherapy. The patient expired within a month as a result of widespread pulmonary metastases. Papillary thyroid carcinoma may metastasize to the uvea bilaterally, cause rapid visual function loss, erode the sclera, and may extend outside the globe similar to choroidal melanoma. This aggressive ocular involvement was associated with a dismal prognosis in our patient.
PMCID: PMC3663067  PMID: 23730117
Choroid; Neoplasm metastasis; Papillary carcinoma; Thyroid gland; Transpupillary thermotherapy
18.  Indocyanine Green Mediated Photothrombosis and High Dose Intravitreal Bevacizumab as Adjuvant Therapy for Isolated Choroidal Metastasis from Breast Cancer 
To report the effectiveness of indocyanine green mediated photothrombosis (IMP) combined with high dose (4 mg/0.16 ml) intravitreal bevacizumab (IVB) as adjunctive therapy for management of isolated choroidal metastasis from breast cancer.
This retrospective interventional case report includes three eyes of two patients with choroidal metastasis from breast cancer. Both patients were submitted to one session of IMP combined with high dose IVB as adjuvant local therapy to systemic chemotherapy. Main outcome measures were tumor response, and fluorescein angiography (FA), optical coherence tomography (OCT), and visual acuity (VA) results.
The first patient was a 47-year-old woman who had undergone radical mastectomy, chemotherapy and radiotherapy 7 years earlier and the second patient was a 70-year-old woman managed with chemotherapy and radiotherapy 16 years before presentation. There was no evidence of systemic metastasis in either case and both suffered from gradually blurred vision. The first patient presented with a unilateral choroidal lesion whereas the second case had bilateral unifocal choroidal lesions which was symptomatic in only one eye. Clinical examination, ultrasonography, FA, and OCT revealed accompanying exudative retinal detachment in all three eyes. OCT 3 to 5 weeks after combined therapy demonstrated complete resolution of subretinal fluid and improved VA in two eyes.
Combined IMP and high-dose IVB seems to be an effective adjunctive treatment to systemic chemotherapy for management of isolated choroidal metastasis from breast cancer.
PMCID: PMC3595580  PMID: 23504577
Avastin; Bevacizumab; Breast Cancer; Choroidal Metastasis; Indocyanine Green Mediated Photothrombosis
19.  Chemo-resistant choriocarcinoma metastatic to colon cured by low-anterior resection 
Journal of Gynecologic Oncology  2011;22(3):203-206.
The role of surgery in the treatment of patients with metastatic choriocarcinoma has diminished. We present a case of chemo-resistant metastatic choriocarcinoma salvaged by surgery. A 48-year-old patient presented with uterine perforation and severe intractable hemorrhage, and histological examination revealed a choriocarcinoma. After 6 years of disease-free state, recurrence occurred in the rectosigmoid colon. Seven cycles of EMACO chemotherapy was administered, and the human chorionic gonadotropin level was normalized. Three months after the chemotherapy, the rectosigmoid colon metastasis progressed. Low anterior resection with lymphadenectomy up to the level of the inferior mesenteric artery was conducted. After the operation, the human chorionic gonadotropin level decreased to within the normal range. There has been no evidence of disease for 13 months since the operation. Local resection of metastases seems to play a significant role in curing the disease in a small subset of patients.
PMCID: PMC3188720  PMID: 21998764
Choriocarcinoma; Colon; Low anterior resection
20.  Mixed Testicular Germ Cell Tumor Presenting as Metastatic Pure Choriocarcinoma Involving Multiple Lung Metastases That Was Effectively Treated with High-dose Chemotherapy 
Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%) of all the testicular germ cell tumors. It is a particularly aggressive variant of non-seminoma tumor, which is characterized by a high serum β-HCG level and multiple lung metastases. The optimal management for this disease remains undefined. We report here on a case of choriocarcinoma with multiple lung metastases, and the patient has achieved continuous remission for 2 years after combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and sequential high-dose chemotherapy with autologous peripheral stem cell rescue.
PMCID: PMC2802842  PMID: 20057969
Neoplasms; Germ cell and embryonal; Testicular choriocarcinoma; High-dose chemotherapy
21.  Metastatic choriocarcinoma to the lumbar spine: Case report and review of literature 
There are few cases of choriocarcinoma metastases to the spine that have been reported. Most occurrences are in women with the gestational form of the tumor, and these now exhibit a very high remission rate with chemotherapeutic treatment, typically circumventing the need for spinal surgery.
Case Description:
In an effort to better understand treatment options for those rare instances when choriocarcinoma does find its way into the spine, we have synthesized a comprehensive literature review on the clinical cases of choriocarcinoma spinal metastases. We also describe our unique experience and decision-making involving the first reported case of surgical treatment of non-gestational choriocarcinoma spinal metastases in a male patient.
Spinal surgery has a limited role in metastatic choriocarcinoma, but there is the potential for improving neurologic decline even in the rare and aggressive male variant of this disease.
PMCID: PMC4258720  PMID: 25525554
Cauda equina; chemotherapy; choriocarcinoma; germinoma; tumor
22.  Small Choroidal Melanoma with Monosomy 3 
To report a patient with small juxtapapillary choroidal melanoma with chromosome 3 monosomy treated with I125 plaque and transpupillary thermotherapy (TTT). A 64-year-old Caucasian male presented with painless blurred vision of the left eye. Ocular examination disclosed a small juxtapapillary choroidal melanocytic tumor with overlying subretinal fluid and orange pigment. Ultrasound showed an elevated choroidal mass of 2 mm thickness with low reflectivity on A-scan and hollowness on B scan, consistent with a small choroidal melanoma. The patient was treated with plaque I125 radiotherapy combined with one session of TTT. Genetic testing of the tumor cells obtained by fine needle aspiration biopsy showed chromosome 3 monosomy. At 1 year after treatment, the tumor was regressed with resolution of subretinal fluid and 20/40 visual acuity. A small choroidal melanoma can manifest monosomy of chromosome 3, a known predictive factor for the development of systemic metastasis.
PMCID: PMC2934721  PMID: 20844685
Choroidal Melanoma; Chromosome 3; Eye; Metastases; Monosomy; Small Choroidal Melanoma
23.  Adjuvant Radiotherapy for Synchronous Bilateral Testicular Seminoma: A Case Report and a Review of the Pertinent Literature 
Case Reports in Urology  2013;2013:241073.
Few cases of synchronous bilateral stage I seminomas have been reported in the world literature. We present a case of bilateral synchronous testicular seminoma, the current literature on the management of stage I seminoma, and the implications for radiotherapy. A forty-year-old man presented with synchronous bilateral classical seminomas, both stage IA. After undergoing bilateral inguinal orchiectomy, he received adjuvant external beam radiotherapy, with a standard paraaortic field. After 18 months of followup, he remains well, without evidence of recurrence. Bilateral germ cell tumors (BGCTs) are reported consistently at a low rate. Bilateral radical inguinal orchiectomy is standard of care, yet some groups have proposed an organ preservation approach. Of the reported cases of bilateral stage I synchronous GCT, with concordant seminoma histology, most of them were treated with bilateral orchiectomy and adjuvant radiotherapy. Although morbidity associated with radiotherapy directed at the abdomen is not negligible, adjuvant paraaortic radiotherapy remains safe and well-tolerated treatment regime. Bilateral synchronous stage I seminoma of the testes is rare. Organ preservation remains investigational. Chemotherapy is probably a reasonable option. We propose that patients with bilateral stage I synchronous GCT, with concordant seminoma histology, should be managed with bilateral orchiectomy, followed by paraaortic radiotherapy.
PMCID: PMC3678426  PMID: 23781383
24.  Age related macular degeneration 
BMJ Clinical Evidence  2007;2007:0701.
Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early-stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression of early- or late-stage age-related macular degeneration; and exudative age-related macular degeneration? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiangiogenesis (using pegaptanib, ranibizumab, interferon alfa-2a, or anecortave acetate), antioxidant vitamins plus zinc, external beam radiation, laser treatment to drusen, photodynamic therapy with verteporfin, submacular surgery, thermal laser photocoagulation, transpupillary thermotherapy.
Key Points
Sight-threatening (late) age related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.85% of cases are atrophic (dry) AMD, but exudative (wet) AMD, marked by choroidal neovascularisation, leads to a more rapid loss of sight.The main risk factor is age. Hypertension, smoking, and a family history of AMD are also risk factors.
High dose antioxidant vitamin and zinc supplementation may reduce progression of moderate AMD, but there is no evidence of benefit in people with no, or mild AMD, or those with established late AMD in both eyes.
CAUTION: Beta-carotene, an antioxidant vitamin used in AMD, has been linked to an increased risk of lung cancer in people at high risk of this disease.
Photodynamic treatment with verteporfin reduces the risk of developing moderate or severe loss of visual acuity and legal blindness in people with vision initially better than 20/100 or 20/200, compared with placebo. Photodynamic treatment is associated with an initial loss of vision and photosensitive reactions in a small proportion of people.
Thermal laser photocoagulation can reduce severe visual loss in people with exudative AMD. It is frequently associated with an immediate and permanent reduction in visual acuity if the lesion involves the central macula, but it remains a proven effective treatment for extrafoveal choroidal neovascularisation. About half of people treated with thermal lasers show recurrent choroidal neovascularisation within 3 years.We don't know whether laser treatment of drusen prevents progression of disease, and it may increase short term rates of choroidal neovascularisation.
Antiangiogenesis treatment using vascular endothelial growth factor (VEGF) inhibitors such as ranibizumab or pegaptanib reduces the risk of moderate vision loss, and may improve vision at 12 and 24 months. Antiangiogenesis treatment using anecortave acetate may be as effective as photodynamic therapy in reducing vision loss.
Studies investigating external beam radiotherapy have given contradictory results, and have failed to show an overall benefit in AMD.
Subcutaneous interferon alfa-2a and submacular surgery have not been shown to improve vision, and are associated with potentially severe adverse effects.
We found no RCT evidence on the effects of transpupillary thermotherapy.
PMCID: PMC2943806  PMID: 19454069
25.  An atypical case of choroidal neovascularization associated with pseudoxanthoma elasticum treated with intravitreal bevacizumab: a case report 
BMC Research Notes  2013;6:530.
Pseudoxanthoma elasticum is an inherited disorder that is associated with accumulation of pathologic elastic fibers in the skin, vascular walls and Bruch’s membrane in the eye. Choroidal neovascularization is one of the most common causes of acute vision loss in these patients. We report an atypical case of suspected choroidal neovascularization associated with pseudoxanthoma elasticum.
Case presentation
A 47-year-old Caucasian woman with pseudoxanthoma elasticum and angioid streaks was referred because of decreased and distorted vision in her right eye of one week’s duration. Visual acuity was 6/12 in the right eye and 6/6 in the left eye. Fundus examination revealed angioid streaks and white intraretinal macular deposits bilaterally. Fluorescein angiography did not reveal any obvious leakage in the right eye while optical coherence tomography revealed subretinal fluid associated with an adjacent intraretinal hyperreflective structure. Autofluoresence imaging showed focal areas of increased autofluorescence corresponding to the deposits in both eyes. Over the following year the patient underwent five intravitreal injections of bevacizumab (Genentech/Roche,US) in the right eye, which resulted in visual acuity improving to 6/9 with regression of the hyperreflective structrure and complete resolution of subretinal fluid.
Traditionally, fluorescein angiography is effective in the detection of choroidal neovascularization in patients with pseudoxanthoma elasticum. In our case, optical coherence tomography revealed subretinal fluid and an adjacent hyperreflective structure while fluorescein angiography did not reveal any obvious leakage. The sole presence of subretinal fluid does not necessarily imply the presence of choroidal neovascularization and certainly retinal pigment epithelium dysfunction could also explain subretinal fluid in these patients. However, the complete absorption of the fluid and the disappearance of the previously evident hyperreflective structure following treatment, led us to suspect choroidal neovascularization as the primary cause of the above findings. The poor natural course of choroidal neovascularization in these patients increases the importance of early detection and should result in the adaptation of a low-threshold strategy concerning the initiation of treatment.
PMCID: PMC3866942  PMID: 24325973
Bevacizumab; Choroidal neovascularization; Pseudoxanthoma elasticum

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