Hereditary Retinoblastoma, Lipoma, and Second Primary Cancers

Benign Tumors in Long-Term Survivors of Retinoblastoma

“…Consistent with SMN findings in hereditary retinoblastoma survivors [19], tumors of soft tissue origin were the most common type of benign tumor. We report a cumulative incidence of 7.6% for lipoma in hereditary survivors at 60 years, confirming our previous findings of heightened prevalence of lipoma in this group [7] and substantiating reported lipoma occurrence in several families and incident cases with hereditary retinoblastoma [8,9]. Previous cytogenetic analyses have shown RB1 loss in lipoma [20,21,22], providing support for an association between germline RB1 mutations in hereditary retinoblastoma and a high incidence of lipoma in these survivors.…”

“…Less is known about the occurrence of subsequent benign neoplasms in retinoblastoma survivors. Previous reports, including one from our cohort, showed an excess of lipoma in patients with hereditary retinoblastoma compared to nonhereditary survivors [7,8,9], suggesting that germline RB1 mutations may also contribute to benign tumor development. However, little is known about the occurrence of other types of benign tumors, and risk factors have not been evaluated, in part due to the fact that benign tumors are not reportable to most cancer registries and thus are not systematically ascertained by most cohorts.…”

Benign Tumors in Long-Term Survivors of Retinoblastoma

“…Consistent with SMN findings in hereditary retinoblastoma survivors [19], tumors of soft tissue origin were the most common type of benign tumor. We report a cumulative incidence of 7.6% for lipoma in hereditary survivors at 60 years, confirming our previous findings of heightened prevalence of lipoma in this group [7] and substantiating reported lipoma occurrence in several families and incident cases with hereditary retinoblastoma [8,9]. Previous cytogenetic analyses have shown RB1 loss in lipoma [20,21,22], providing support for an association between germline RB1 mutations in hereditary retinoblastoma and a high incidence of lipoma in these survivors.…”

“…Less is known about the occurrence of subsequent benign neoplasms in retinoblastoma survivors. Previous reports, including one from our cohort, showed an excess of lipoma in patients with hereditary retinoblastoma compared to nonhereditary survivors [7,8,9], suggesting that germline RB1 mutations may also contribute to benign tumor development. However, little is known about the occurrence of other types of benign tumors, and risk factors have not been evaluated, in part due to the fact that benign tumors are not reportable to most cancer registries and thus are not systematically ascertained by most cohorts.…”

Radiation Retinopathy and Benign Lymphoproliferative Orbital Tumor Presenting 47 Years After Treatment of Hereditary Retinoblastoma

“…20 Hereditary retinoblastoma is also associated with an increased risk of developing secondary benign lipomas, also likely associated with RB1 mutation. 21 However, extensive literature review revealed no published cases of secondary benign lymphoproliferative tumors in the setting of retinoblastoma postradiation and/or chemotherapy (as was found in our patient). There have been studies indicating that patients with 13q deletions are at possible higher risk of developing B-cell lymphoproliferative disorders, 22,23 but how this may relate to our patient remains unclear at this time.…”

Clustering of deletions on chromosome 13 in benign and low‐malignant lipomatous tumors

“…The conclusion that the RB1 ‐gene is not the main target for the deletions is supported by the lack of correlation between LOH at the RB1 ‐locus and reduced RB1 ‐expression in breast, prostate and head and neck tumors,21, 26, 27 although contrasting reports have been reported for some breast28 and liver cancers 29. Interestingly, an association between a constitutional RB1 ‐mutation and the development of lipoma has been suggested from an epidemiological study of 556 patients with hereditary retinoblastoma 30. Although inactivation of the RB1 ‐gene could not be excluded in the present study, the clustering of breaks and deletions opens the possibility for the presence and involvement of other target genes, which are located close to RB1 .…”

Benign Tumors in Long-Term Survivors of Retinoblastoma

“…Consistent with SMN findings in hereditary retinoblastoma survivors [19], tumors of soft tissue origin were the most common type of benign tumor. We report a cumulative incidence of 7.6% for lipoma in hereditary survivors at 60 years, confirming our previous findings of heightened prevalence of lipoma in this group [7] and substantiating reported lipoma occurrence in several families and incident cases with hereditary retinoblastoma [8,9]. Previous cytogenetic analyses have shown RB1 loss in lipoma [20,21,22], providing support for an association between germline RB1 mutations in hereditary retinoblastoma and a high incidence of lipoma in these survivors.…”

“…Less is known about the occurrence of subsequent benign neoplasms in retinoblastoma survivors. Previous reports, including one from our cohort, showed an excess of lipoma in patients with hereditary retinoblastoma compared to nonhereditary survivors [7,8,9], suggesting that germline RB1 mutations may also contribute to benign tumor development. However, little is known about the occurrence of other types of benign tumors, and risk factors have not been evaluated, in part due to the fact that benign tumors are not reportable to most cancer registries and thus are not systematically ascertained by most cohorts.…”

Radiation Retinopathy and Benign Lymphoproliferative Orbital Tumor Presenting 47 Years After Treatment of Hereditary Retinoblastoma

“…20 Hereditary retinoblastoma is also associated with an increased risk of developing secondary benign lipomas, also likely associated with RB1 mutation. 21 However, extensive literature review revealed no published cases of secondary benign lymphoproliferative tumors in the setting of retinoblastoma postradiation and/or chemotherapy (as was found in our patient). There have been studies indicating that patients with 13q deletions are at possible higher risk of developing B-cell lymphoproliferative disorders, 22,23 but how this may relate to our patient remains unclear at this time.…”

Clustering of deletions on chromosome 13 in benign and low‐malignant lipomatous tumors

“…The conclusion that the RB1 ‐gene is not the main target for the deletions is supported by the lack of correlation between LOH at the RB1 ‐locus and reduced RB1 ‐expression in breast, prostate and head and neck tumors,21, 26, 27 although contrasting reports have been reported for some breast28 and liver cancers 29. Interestingly, an association between a constitutional RB1 ‐mutation and the development of lipoma has been suggested from an epidemiological study of 556 patients with hereditary retinoblastoma 30. Although inactivation of the RB1 ‐gene could not be excluded in the present study, the clustering of breaks and deletions opens the possibility for the presence and involvement of other target genes, which are located close to RB1 .…”

Benign Tumors in Long-Term Survivors of Retinoblastoma

“…Consistent with SMN findings in hereditary retinoblastoma survivors [19], tumors of soft tissue origin were the most common type of benign tumor. We report a cumulative incidence of 7.6% for lipoma in hereditary survivors at 60 years, confirming our previous findings of heightened prevalence of lipoma in this group [7] and substantiating reported lipoma occurrence in several families and incident cases with hereditary retinoblastoma [8,9]. Previous cytogenetic analyses have shown RB1 loss in lipoma [20,21,22], providing support for an association between germline RB1 mutations in hereditary retinoblastoma and a high incidence of lipoma in these survivors.…”

“…Less is known about the occurrence of subsequent benign neoplasms in retinoblastoma survivors. Previous reports, including one from our cohort, showed an excess of lipoma in patients with hereditary retinoblastoma compared to nonhereditary survivors [7,8,9], suggesting that germline RB1 mutations may also contribute to benign tumor development. However, little is known about the occurrence of other types of benign tumors, and risk factors have not been evaluated, in part due to the fact that benign tumors are not reportable to most cancer registries and thus are not systematically ascertained by most cohorts.…”

Radiation Retinopathy and Benign Lymphoproliferative Orbital Tumor Presenting 47 Years After Treatment of Hereditary Retinoblastoma

“…20 Hereditary retinoblastoma is also associated with an increased risk of developing secondary benign lipomas, also likely associated with RB1 mutation. 21 However, extensive literature review revealed no published cases of secondary benign lymphoproliferative tumors in the setting of retinoblastoma postradiation and/or chemotherapy (as was found in our patient). There have been studies indicating that patients with 13q deletions are at possible higher risk of developing B-cell lymphoproliferative disorders, 22,23 but how this may relate to our patient remains unclear at this time.…”

Clustering of deletions on chromosome 13 in benign and low‐malignant lipomatous tumors

“…The conclusion that the RB1 ‐gene is not the main target for the deletions is supported by the lack of correlation between LOH at the RB1 ‐locus and reduced RB1 ‐expression in breast, prostate and head and neck tumors,21, 26, 27 although contrasting reports have been reported for some breast28 and liver cancers 29. Interestingly, an association between a constitutional RB1 ‐mutation and the development of lipoma has been suggested from an epidemiological study of 556 patients with hereditary retinoblastoma 30. Although inactivation of the RB1 ‐gene could not be excluded in the present study, the clustering of breaks and deletions opens the possibility for the presence and involvement of other target genes, which are located close to RB1 .…”