Bilateral hearing loss preceding rhomboencephalitis - a hint for Kelch-like 11 syndrome.

BACKGROUND: Paraneoplastic neurological syndromes have diverse clinical presentations and offer an opportunity for early diagnosis of malignancy and treatment. Recently, a new paraneoplastic syndrome associated with seminoma was described, consisting of rhombencephalitis with antibodies targeting the Kelch-like protein 11 (KLHL11). Questions were raised as to the spectrum of clinical symptoms and strength of association to seminoma. METHODS: We present a 45-year-old man with bilateral sensorineural hearing loss, vertigo, and progressive ataxia. An extensive diagnostic workup led to the diagnosis of anti-KLHL11 paraneoplastic syndrome based on an immunofluorescence assay showing a typical pattern and a confirmatory serological assay. As a result, the patient underwent a meticulous search for an underlying seminoma. RESULTS: Although initially, all images were interpreted as negative, a revision of the positron emission tomography-CT (PET-CT) examination identified a small mediastinal suspicious mass. The mass was resected, and pathological examination confirmed it to be an extra-testicular seminoma. CONCLUSIONS: Patients presenting with progressive sensorineural hearing loss, vertigo, and ataxia should be evaluated for KLHL11 paraneoplastic syndrome. Furthermore, we support a strong association between anti-KLH11 rhombencephalitis and an underlying seminoma and recommend a thorough search for an undiagnosed germ cell tumor in these patients.

[Pulmonary vein stenosis with pulmonary infarction secondary to primary mediastinal seminoma: a case report].

Pulmonary vein stenosis is a rare condition that is often underdiagnosed and misdiagnosed. The clinical and radiologic manifestations are unspecific such as cough, hemoptysis and pulmonary lesions and are therefore difficult to distinguished with pneumonia and tuberculosis. The present study is a successful case report of pulmonary vein stenosis and pulmonary infraction secondary to mediastinal seminoma. This case suggested that pulmonary vein stenosis should be considered when a mediastinal mass is accompanied by pulmonary opacites that cannot be explained by common causes such as infection.

Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis.

A 37-year-old man with a history of seminoma presented with vertigo, ataxia, and diplopia. An autoantibody specific for kelch-like protein 11 (KLHL11) was identified with the use of programmable phage display. Immunoassays were used to identify KLHL11 IgG in 12 other men with similar neurologic features and testicular disease. Immunostaining of the patient's IgG on mouse brain tissue showed sparse but distinctive points of staining in multiple brain regions, with enrichment in perivascular and perimeningeal tissues. The onset of the neurologic syndrome preceded the diagnosis of seminoma in 9 of the 13 patients. An age-adjusted estimate of the prevalence of autoimmune KLHL11 encephalitis in Olmsted County, Minnesota, was 2.79 cases per 100,000 men. (Funded by the Rochester Epidemiology Project and others.).

Bone Marrow Metastasis from Testicular Seminoma Coexisting with Treatment-Associated Acute Myeloid Leukemia.

BACKGROUND: According to the 2017 WHO classification, therapy related myeloid neoplasms refer to therapy-related acute myeloid leukemia, therapy-related myelodysplastic syndromes, and therapy-related myelodysplastic/ myeloproliferative neoplasms, which happen as a belated occurring complication of chemotherapy and/or radiation therapy due to prior iatrogenic exposure of mutagenic agents. RESULTS: Herein, we present a very rare case of bone marrow metastasis from testicular seminoma coexisting with treatment-associated acute myeloid leukemia. CONCLUSIONS: This paper highlights the rare and easily misdiagnosed morphological feature of bone marrow. In these situations, clinical history, scrupulous examination of blood and bone marrow smears, immunophenotyping, and bone marrow biopsy are necessary to establish a correct diagnosis.

Paraneoplastic Demyelinating Inflammatory Neuropathy Revealing Metastatic Seminoma: A Case Report.

Paraneoplastic neurological syndrome (PNS) is uncommon and not well known. PNS can reveal cancer, but its role in seminomas has not been described explicitly. We report the case of a 36-year-old man with unremarkable medical history and no comorbidities who was diagnosed with a retroperitoneal metastatic seminoma. The patient's general condition deteriorated, and he developed progressive neurological palsy without other clinical anomalies. Electromyography revealed demyelinating, non-lengthy neuropathy. Guillain-Barré syndrome was initially suspected. However, a positron emission tomography scan revealed a retroperitoneal mass, and blood markers revealed increased human chorionic gonadotropin. The patient was diagnosed with PNS, and a computed tomography-guided biopsy revealed a metastatic seminoma without a primary tumor. No circulating neural antibodies were detected. Human polyvalent immunoglobulin was simultaneously administered with chemotherapy. After three cycles of a cisplatin-etoposide-bleomycin, a complete biological and metabolic response rate was observed, and his neurological symptoms rapidly improved. Four years later, the patient responded completely, without any neurological complaints. Paraneoplastic demyelinating inflammatory neuropathy can lead to advanced seminoma diagnosis. Prompt management of seminomas with cisplatin-based regimens provides the best chance of cure for both advanced seminoma and paraneoplastic syndrome.

Abdominal cocoon with bilateral cryptorchidism and seminoma in the right testis: a case report and review of literature.

BACKGROUND: Abdominal cocoon is a rare peritoneal lesion and is difficult to diagnose because of its lack of special clinical manifestations. Until now, there is no case report of abdominal cocoon combined with cryptorchidism and seminoma. CASE PRESENTATION: A case of abdominal cocoon with cryptorchidism and seminoma was diagnosed and treated in our hospital. The patient had no symptoms except occasional abdominal pain. He underwent laparoscopy because of bilateral cryptorchidism and seminoma in the right testis. During the surgery, he was diagnosed with abdominal cocoon due to the thick fibrous tissues which was tightly adhered and encased part of intestine like a cocoon. Enterolysis and bilateral cryptochiectomy were performed after the diagnosis and nutritional and symptomatic support was provided after the surgery. The patient recovered well and was discharged soon. The postoperative pathological examination confirmed the presence of bilateral cryptorchidism and seminoma in the patient's right testis. CONCLUSION: There are only a handful of cases where a patient has both abdominal cocoon and cryptorchidism. Since the etiologies of both diseases remain unknown, further research is required to investigate effective diagnosis and treatment for the diseases and explore the potential connection between the two diseases.

Seminoma with Neoplastic Meningitis Treated with Craniospinal Irradiation.

Pure seminoma is a histological subtype of testicular cancer that accounts for 50% of testicular germ cell tumors. It has a very low rate of metastasis to the central nervous system, with only one previously reported case of neoplastic meningitis (cancer that has spread to the cerebrospinal fluid). Traditionally, neoplastic meningitis has an ominous prognosis when associated with primary tumors that commonly spread to the leptomeninges, like breast and lung. This article highlights a unique case of pure seminoma with neoplastic meningitis and illustrates the effectiveness of craniospinal irradiation as a treatment modality.

Prevalence and Management of Incidental Small Testicular Masses Discovered on Ultrasonographic Evaluation of Male Infertility.

PURPOSE: We report the safety of surveillance of small testicular masses incidentally discovered during evaluation of male infertility. MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database to identify patients with male infertility found to have incidental small testicular masses (hypoechoic lesions less than 10 mm) on scrotal ultrasound. The men were offered close surveillance with interval imaging and office followup. Patient and imaging characteristics were collected to compare the surveillance and surgical groups with additional comparisons between benign and malignant pathologies to elucidate predictors of underlying malignancy. RESULTS: Of 4,088 men in whom scrotal ultrasound was completed for male infertility evaluation 120 (2.9%) were found to have a subcentimeter testicular mass. Average followup was 1.30 years (range 0.1 to 16.9). A total of 18 men (15%) proceeded to extirpative surgery while 102 remained on surveillance at last followup. In those with at least 1 month of followup the mean lesion growth rate was -0.01 mm per year. Reasons for surgery included testicular exploration for infertility, mass growth, positive tumor markers, history of testis cancer, concerning imaging characteristics and patient choice. Six of the 18 men who underwent surgery were found to have malignancy, which was seminoma in all. All malignant lesions were greater than 5 mm on initial imaging and demonstrated vascularity, although size and vascularity were not significantly different from those of benign lesions on final pathology findings. No patients demonstrated advanced or recurrent disease. CONCLUSIONS: Small testicular masses are not uncommon, especially in the infertile male population. Most of these masses do not show significant growth during long-term evaluation and can be safely surveilled with close followup.

Multidisciplinary management of testicular cancer complicated by thrombosis of the inferior vena cava: a case report.

INTRODUCTION: Testicular cancer is a rare disease, most commonly seen in young adults. It represents 1% of solid cancers in men. Inferior vena cava (IVC) thrombosis remains a rare complication of testicular cancer and is often associated with a high risk of pulmonary embolism (PE). CASE REPORT: The authors report a case of a 26-year-old man presenting with advanced testicular cancer, left-sided retroperitoneal metastasis and parietal infiltration of the IVC complicated with thrombosis of the left iliac vein and the IVC, both responsible for PE. DISCUSSION: A multidisciplinary management which included curative excision of the lesions, placement of a temporary IVC filter and adjuvant chemotherapy permitted an optimal approach. No complications occurred and the post-operative healing was uneventful. No recurrences were observed on the long-term follow-up. CONCLUSIONS: IVC Thrombosis is a rare complication that should be taken into consideration when diagnosing testicular cancer. Prompt diagnosis is crucial to minimize the risk of PE which can be life-threatening.

Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma.

BACKGROUND: Bleomycin-induced lung injury, a major complication of chemotherapy for germ cell tumors, occasionally fails to respond to the standard treatment with corticosteroids and develops into severe respiratory insufficiency. Little is known about salvage treatment for refractory cases. CASE PRESENTATION: A 63-year-old man who had been diagnosed with stage I seminoma and undergone a high orchiectomy 1 year previously developed swelling of his left iliac lymph node and was diagnosed with a recurrence of the seminoma. He was administered a standard chemotherapy regimen of cisplatin, etoposide, and bleomycin. At the end of second cycle, he developed a dry cough and fever that was accompanied by newly-identified bilateral infiltrates on chest X-ray. Despite initiation of oral prednisolone, his exertional dyspnea and decline in pulmonary functions continued to be aggravated. High-dose pulse treatment with methylprednisolone was introduced and improved his symptoms and radiologic findings. However, the maintenance dose of oral prednisolone allowed reactivation of the disease with evidence of newly-developed bilateral lung opacities on high-resolution CT scans. Considering his glucose intolerance and cataracts as complications of corticosteroid treatment, administration of pirfenidone was initiated with the patient's consent. Pirfenidone at 1800 mg/day was well tolerated, and resolved his symptoms and abnormal opacities on a chest CT scan. Subsequently, the dose of prednisolone was gradually tapered without worsening of the disease. At the most recent follow-up, he was still in complete remission of seminoma with a successfully tapered combination dose of prednisolone and pirfenidone. CONCLUSIONS: Pirfenidone, a novel oral agent with anti-inflammatory and -fibrotic properties, should be considered as a salvage drug for refractory cases of bleomycin-induced lung injury.

Paraneoplastic neurological syndrome due to burned-out testicular tumor showing hot cross-bun sign.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are rare remote effect of cancer. The antibodies and tumors associated with PNS have been well described, but there are still many clinically suspected cases in which no tumor or antibody can be identified. This is the first report of PNS showing hot cross-bun sign and caused by exceptionally rare underlying malignancy, such as burned-out testicular tumor. CASE PRESENTATION: A 42-year-old man presented subacute progression of hearing loss and cerebellar ataxia. Cerebrospinal fluid showed continuous inflammation and magnetic resonance imaging (MRI) revealed cerebellar atrophy and hot cross-bun sign. Resection of tumors improved both laboratory findings and neurological signs and their pathology was seminoma. CONCLUSION: Seminoma can cause PNS showing 8th cranial nerve palsy, cerebellar, and brainstem atrophy with hot cross-bun sign on MRI study. Extensive screening for onconeural antibodies was negative and thereby suggested that unknown antibodies worked for both antitumor immunity and induction of PNS.

[Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy.

Factor V Leiden mutation triggering four major complications to standard dose cisplatin-chemotherapy for testicular seminoma: a case report.

BACKGROUND: Major life-threatening complications secondary to cisplatin-based chemotherapy are rare in patients with testicular germ cell tumour (GCT). The incidence of complications increases with dosage of chemotherapy and with a variety of patient-related as well as disease-related conditions. We here report the first case of GCT experiencing as many as four major complications most of which can be explained by the conjunction of several predispositions. CASE PRESENTATION: A 48 year old patient with testicular seminoma and bulky retroperitoneal and mediastinal metastases underwent cisplatin based chemotherapy. During the third cycle of chemotherapy, he developed thrombosis of the central venous port device, subtotal splenic infarction, and Bleomycin induced pneumonitis (BIP). Three months after completion of therapy, he was struck by thalamic infarction. Genetic testing then revealed heterozygote mutation of Factor V Leiden (FVL). He received full-dose warfarin anticoagulation treatment and steroid treatment for BIP. 18 months thereafter, the patient is still disease-free, oncologically. Neurological symptoms have disappeared, but pulmonary dysfunction persists with a vital capacity of 50%. CONCLUSION: The unique co-incidence of four major complications occurring in this patient were obviously triggered by the genetically determined predisposition of the patient to thrombotic events (FVL). Additionally, several patient-related and disease-related conditions contributed to the unique pattern of complications, i.e. (1) the slightly advanced age (48 years), (2) the prothrombotic condition caused by the disease of cancer, (3) the central venous port device, (4) retroperitoneal bulky metastasis, and (5) cisplatin chemotherapy. Whether or not FVL contributed to the pulmonary fibrosis as well, remains elusive. Practically, in the case of one major vascular complication during cisplatin chemotherapy at standard dose, genetic testing for hereditary thrombophilia should be considered. Thus, precautions for preventing further complications could be initiated.

Malignant seminoma in two unilaterally cryptorchid stallions.

Two unilateral cryptorchid stallions were referred to the clinic because of chronic debilitating condition with emaciation. Rectal examination, and ultrasound and gross examination revealed in both animals an abdominal mass, caudally of the kidney, and multiple nodules spread over the abdomen. Histologic analysis revealed an intra-abdominal malignant seminoma with intraperitoneal and renal metastasis. Interestingly, a seminoma was also present in the descended testis of the draught horse.

[Testicular nodules of infertile men and contrast enhanced ultrasonography: preliminary study]. / Nodules testiculaires de l'homme infertile et échographie de contraste: étude préliminaire.

INTRODUCTION: The incidence of testicular nodules discovered during infertility evaluation is increasing. These nodules are suspicious of malignancy. There is no paraclinical examination which allows histological orientation to these nodules. The recommendations propose priority treatment by total orchidectomy. PATIENTS AND METHODS: Through a retrospective cohort study of infertile patients, our goal is to study the enhancement of testicular nodules after injection of ultrasound contrast. The secondary objective is to determine whether CEUS may argue in favor of conservative treatment. From june 2010 to march 2013, 24 patients had underwent ultrasound contrast study of abnormal testicular parenchyma detected prior to infertility evaluation carried ultrasound. The characteristics of ultrasound enhancement were correlated with the pathological findings of surgical patients and proposed treatments (surgery or surveillance). RESULTS: Fifteen patients were followed up, 9 were operated (7 partial orchidectomies, 2 total orchidectomies). Histological analysis found four Leydig cell tumors, 2 Sertoli cell tumors and 3 seminomas. No adverse changes were noted during the follow-up. This study showed a typical semiology of early, intense and homogeneous enhancement with a phenomenon of wash in 100% of Leydig cell tumors. All Leydig cell tumors have been treated by partial orchidectomy. Seminomas have intense enhancement in 100% of cases. There was a phenomenon of wash in 2 out of 3 cases. When a wash in was described, it was always described as heterogeneous. All seminomas were finally treated by total orchidectomy. The sensitivity and positive predictive value of ultrasound intense enhancement for the diagnosis of testicular cancer was 89% (Se) and 80% (PPV). CONCLUSION: There is a semiology of ultrasound enhancement of testicular nodules with features that can guide in favor of a malignant tumor, seminoma or Leydig cell tumor. If a prospective study was undertaken, these arrangements could guide us to treatments promoting preservation of the testicular parenchyma.

1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma.

BACKGROUND: Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied.The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. CASE PRESENTATION: A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed "cannon ball" pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. CONCLUSION: The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values.

Inferior vena cava prosthetic replacement in a patient with horseshoe kidney and metastatic testicular tumor: technical considerations and review of the literature.

BACKGROUND: Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the testis are a rare cancer, with an estimated incidence of 56.3 per million white males and 10 per million black males in the United States.The association between non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about 1.3% of patients requiring retroperitoneal lymph node dissection. To our knowledge, no cases have been reported in which replacement of the IVC was also necessary. CASE PRESENTATION: We report the case of a 22-year-old man with horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the wall of the inferior vena cava.Following post-chemotherapy retroperitonal lymph node dissection, the inferior vena cava was replaced with an expanded polytetrafluoroethylene graft.At 2-years follow-up, the patient was in good health and the graft was patent. No clinical or diagnostic signs of renal impairment or recurrence of neoplastic disease were noted. CONCLUSION: Radical surgery is warranted in patients with non-seminomatous germ cell tumor metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is required, and the situation is further complicated by horseshoe kidney, as in this case, surgical technique will rely on multidisciplinary surgical treatment planning by a team composed of urologists, vascular surgeons and oncologists.

Sperm cryopreservation before testicular cancer treatment and its subsequent utilization for the treatment of infertility.

AIMS: In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. METHODS: Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5%) was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. RESULTS: A total of 557 men have decided to freeze their semen before cancer treatment. Azoospermia was diagnosed in 34 men (6.1%), and semen was cryopreserved in 532 patients. Seminoma was diagnosed in 283 men (54.1%) and nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. CONCLUSION: The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.