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Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

Williams PA, Bhaijee F, Rezeanu L, Hamilton RD, Vijayakumar S - J Investig Med High Impact Case Rep (2013)

Bottom Line: Radiation-induced papillary thyroid carcinoma followed 13 years later.Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter.More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells.

View Article: PubMed Central - PubMed

Affiliation: University of Mississippi Medical Center, Jackson, MS, USA.

ABSTRACT

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies.

Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter.

Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

No MeSH data available.


Related in: MedlinePlus

Soft tissue osteosarcoma in 2010, in the right cervicothoracic paraspinal musculature.
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fig2-2324709613484302: Soft tissue osteosarcoma in 2010, in the right cervicothoracic paraspinal musculature.

Mentions: At the age of 30, the patient presented with a 1-year history of a painful enlarging right posterior cervicothoracic shoulder mass in the paraspinal trapezius musculature that extended medially to the posterior spinous processes (Figure 2). Excisional biopsy revealed an 8.3 cm small cell soft tissue osteosarcoma; this was treated with 2 cycles of high-dose methotrexate followed by adriamycin and cisplatin (Figure 3). Follow-up computed tomography showed residual tumor at the biopsy site. This was re-excised just over a year after the initial biopsy. Histopathologic evaluation demonstrated a 10.5 cm osteosarcoma with 40% tumor necrosis; a positive surgical margin at the trapezius muscle prompted a repeat resection with partial scapulectomy. Six months later, solitary metastatic osteosarcoma was found in the pancreas with subsequent widespread abdominal organ involvement. He underwent additional high-dose methotrexate, adriamycin, and cisplatin therapy, followed by exploratory laparotomy for attempted resection of pancreatic and adrenal masses. Multiple liver and mesenteric masses were found perioperatively and the decision was made not to proceed with surgery. DNA sequence analysis from a blood sample identified a germline heterozygous c.3224delT deletion in exon 15 of the APC gene. This deletion is known to cause a frameshift mutation and accumulation of truncated proteins. Since the heterozygous mutation caused the classic FAP phenotype, this case is consistent with an autosomal dominant inheritance pattern that also fits the positive maternal family history.


Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

Williams PA, Bhaijee F, Rezeanu L, Hamilton RD, Vijayakumar S - J Investig Med High Impact Case Rep (2013)

Soft tissue osteosarcoma in 2010, in the right cervicothoracic paraspinal musculature.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4528792&req=5

fig2-2324709613484302: Soft tissue osteosarcoma in 2010, in the right cervicothoracic paraspinal musculature.
Mentions: At the age of 30, the patient presented with a 1-year history of a painful enlarging right posterior cervicothoracic shoulder mass in the paraspinal trapezius musculature that extended medially to the posterior spinous processes (Figure 2). Excisional biopsy revealed an 8.3 cm small cell soft tissue osteosarcoma; this was treated with 2 cycles of high-dose methotrexate followed by adriamycin and cisplatin (Figure 3). Follow-up computed tomography showed residual tumor at the biopsy site. This was re-excised just over a year after the initial biopsy. Histopathologic evaluation demonstrated a 10.5 cm osteosarcoma with 40% tumor necrosis; a positive surgical margin at the trapezius muscle prompted a repeat resection with partial scapulectomy. Six months later, solitary metastatic osteosarcoma was found in the pancreas with subsequent widespread abdominal organ involvement. He underwent additional high-dose methotrexate, adriamycin, and cisplatin therapy, followed by exploratory laparotomy for attempted resection of pancreatic and adrenal masses. Multiple liver and mesenteric masses were found perioperatively and the decision was made not to proceed with surgery. DNA sequence analysis from a blood sample identified a germline heterozygous c.3224delT deletion in exon 15 of the APC gene. This deletion is known to cause a frameshift mutation and accumulation of truncated proteins. Since the heterozygous mutation caused the classic FAP phenotype, this case is consistent with an autosomal dominant inheritance pattern that also fits the positive maternal family history.

Bottom Line: Radiation-induced papillary thyroid carcinoma followed 13 years later.Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter.More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells.

View Article: PubMed Central - PubMed

Affiliation: University of Mississippi Medical Center, Jackson, MS, USA.

ABSTRACT

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies.

Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter.

Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

No MeSH data available.


Related in: MedlinePlus