ABSTRACT
Recently, nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we report the case of a novel SDHB mutation (L157X) in a Japanese patient with abdominal paraganglioma following malignant lung metastasis. In addition, we identified an asymptomatic carrier of the SDHB mutation in this family.
Subject(s)
Paraganglioma/genetics , Retroperitoneal Neoplasms/genetics , Succinate Dehydrogenase/genetics , Adult , Asian People/genetics , Female , Germ-Line Mutation , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Male , Middle Aged , Pedigree , Retroperitoneal Neoplasms/pathologyABSTRACT
A 76-year-old man had been treated with maximum androgen blockade therapy for a poorly-differentiated prostate adenocarcinoma (T3cN1M0, prostate specific antigen (PSA) 65 ng/ml, Gleason Score 4+5=9) since September 2002. By August 2003, his serum PSA levels were undetectable and the lymph node swelling had vanished. However, in December 2004, his serum PSA levels started rising gradually up to 0.66 ng/ml. Radiation therapy on the prostate was then performed (66 Gy). At that time, no metastasis was detected by computed tomography and bone scintigraphy. In August 2005, multiple bone metastases were detected. Immunohistochemical examination of a biopsy specimen from the bone lesion revealed a small cell carcinoma/neuroendocrine cell carcinoma. He died with undetectable PSA levels (less than 0.008 ng/ml) in December 2005. The autopsy showed multiple organ metastases including bone, liver, lungs and others. The immunohistochemical examination revealed pure small cell carcinoma in all metastatic lesions. A precise histological examination of the lungs using a 1 cm serial section could not reveal any tumors compatible with primary lung cancer. We concluded from the clinical history and autopsy findings that his initial poorly-differentiated adenocarcinoma of the prostate dedifferentiated into a pure small cell carcinoma with neuroendocrine differentiation.