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Why are epididymal tumours so rare?

ABSTRACT: Epididymal tumour incidence is at most 0.03% of all male cancers. It is an enigma why the human epididymis does not often succumb to cancer, when it expresses markers of stem and cancer cells, and constitutively expresses oncogenes, pro-proliferative and pro-angiogenic factors that allow tumour cells to escape immunosurveillance in cancer-prone tissues. The privileged position of the human epididymis in evading tumourigenicity is reflected in transgenic mouse models in which induction of tumours in other organs is not accompanied by epididymal neoplasia. The epididymis appears to: (i) prevent tumour initiation (it probably lacks stem cells and has strong anti-oxidative mechanisms, active tumour suppressors and inactive oncogene products); (ii) foster tumour monitoring and destruction (by strong immuno-surveillance and -eradication, and cellular senescence); (iii) avert proliferation and angiogenesis (with persistent tight junctions, the presence of anti-angiogenic factors and misplaced pro-angiogenic factors), which together (iv) promote dormancy and restrict dividing cells to hyperplasia. Epididymal cells may be rendered non-responsive to oncogenic stimuli by the constitutive expression of factors generally inducible in tumours, and resistant to the normal epididymal environment, which mimics that of a tumour niche promoting tumour growth. The threshold for tumour initiation may thus be higher in the epididymis than in other organs. Several anti-tumour mechanisms are those that maintain spermatozoa quiescent and immunologically silent, so the low incidence of cancer in the epididymis may be a consequence of its role in sperm maturation and storage. Understanding these mechanisms may throw light on cancer prevention and therapy in general.

SUBMITTER: Yeung CH

PROVIDER: S-EPMC3720153 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other

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Project description:BACKGROUND: Epstein-Barr Virus (EBV) associated lymphoproliferative disorders are encountered in immunodeficiency states. Amongst these, primary CNS lymphoma in HIV/AIDS patients is relatively rare and represents a therapeutic challenge. MATERIALS AND METHODS: This report was generated from patient's medical records throughout hospitalizations and outpatient visits. RESULTS: A 20-year-old female with congenitally acquired HIV and poor medication compliance presented with severe headaches and mild cranial nerve deficits. HIV viral load at presentation was 89,976/ml with CD4 count of 4/uL. Head MRI revealed 3-cm thick-walled ring-enhancing lesion in right basal ganglia. Serum titers for toxoplasmosis were negative. EBV DNA was detected by PCR in CSF without peripheral viremia. Imaging with thallium scan and MRI findings in combination with EBV PCR positive CSF allowed for the presumptive diagnosis of EBV-associated primary CNS lymphoma. Highly active anti-retroviral therapy (HAART) was reinitiated. Karnofsky score was 90%, thus chemotherapy was offered to optimize chance of cure. Agents of choice were high-dose Methotrexate for CNS penetration/anti-lymphoma activity and Rituximab. Within the next 5 months she received 8 cycles of alternating Methotrexate (4000 mg/m2/dose on Day 1) and Rituximab (375 mg/m2/dose on Day 8). Supportive care included leucovorin rescue and urine alkalinization. Therapy was tolerated well without sepsis episodes during neutropenia. Her headaches and neurological deficits resolved after the first cycle of therapy. Serial imaging demonstrated substantial and continuous regression of the lymphoma lesion. No adjunctive radiotherapy was administered. Patient remains in remission 18 months after diagnosis, despite fluctuating viral loads and CD4 counts due to the poor HAART compliance. No chronic hypogammaglobulinemia resulted from therapy to date. CONCLUSION: Given the observed results and acceptable toxicity profile, methotrexate and rituximab combination may be effective and should be considered in addition to HAART for treating EBV-associated CNS lymphoma in young patients with minimal comorbidities and underlying HIV/AIDS. INTRODUCTION: Pediatric pineal parenchymal tumors of intermediate differentiation (PPTID, WHO grade II or III) are extremely uncommon. Appropriate therapy has not been defined. We present three new cases of pediatric PPTID and 8 cases in patients under age 45 identified in a literature review. METHODS: This study utilized the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) (http://www.prisma-statement.org.). RESULTS: We diagnosed two children (female age 5 y, male age 14 y) with PPTID in the pineal region and negative work-up for metastases. Both underwent gross total resection (GTR). Pathologic evaluation was consistent with PPTID grade II in each. Both were treated with local radiation therapy via protons to 50.4 CGE. The first patient (case 1) is now 4 years since diagnosis with no evidence of disease (NED) and the second (case 2) is 8 months after surgery and NED. Our third case (male age 15 y) was diagnosed with PPTID grade III with drop metastases in the thecal sac (case 3). He was treated with craniospinal and boost radiation and multiagent chemotherapy but relapsed with leptomeningeal disease near the conus 2 years after diagnosis. Our literature review identified 8 cases of PPTID in patients under age 45, described in Table 1 (cases 4-11). There were broad treatment strategies from GTR only to craniospinal radiation and multiagent chemotherapy. While the therapy varied, the outcome for those with non-metastatic grade II tumors was good. Grade III tumors were associated with metastatic disease and a worse outcome. DISCUSSION: With very few cases, definitive recommendations for therapy are impossible. For PPTID grade II, GTR alone may be sufficient. PPTID grade III should be considered for more aggressive therapy.

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Why are epididymal tumours so rare?

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