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Presented by William Westra, M.D. and prepared by Julie M. Wu, M.D.
Case 6: 60 year-old man with multinodular hyperplasia and an incidental 1 cm thyroid nodule.
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1. Question
Week 327: Case 6
60 year-old man with multinodular hyperplasia and an incidental 1 cm thyroid nodule.images/jmw100807/6.1.jpg
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images/jmw100807/6.4b.jpgCorrect
Answer: Metastatic renal cell carcinoma
Histology: The thyroid shows multinodular adenomatoid hyperplasia, but one of the nodules is conspicuous for its composition of clear cells. The clear cells maintain a nested pattern of growth. There is a rich but delicate vascular network. The follicles are packed with red blood cells. The nuclei are small with condensed chromatin. Mitotic figures are not observed. Immunohistochemical studies were performed. The tumor cells are not immunoreactive for thyroglobulin, TTF1 or PAX2. An RCC immunostaining shows focal equivocal membrane staining.
Discussion: Prominent clear cell change can be encountered in various types of primary thyroid tumors. Cytoplasmic clearing is not uncommon for Hurthle cell neoplasm where and is believed to reflect mitochondrial swelling and degeneration. Clear cell change in follicular and papillary neoplasm usually reflects the cytoplasmic accumulation of glycogen. In the present case, the absence of staining for TTF1 and thyroglobulin raised the possibility of a tumor of non-follicular origin.
Metastatic involvement of the thyroid gland is not unusual, but it is usually seen in the context of widespread metastases. Metastatic involvement of the thyroid gland as a sentinel event in a patient with an occult primary tumor is a much rarer occurrence. In this situation, the most common primary tumor is renal cell carcinoma followed by colorectal carcinoma and malignant melanoma. In effect, metastatic renal cell carcinoma should always be included in the differential diagnosis of clear cell tumors involving the thyroid.
There are several morphologic features that are consistently present in metastatic renal cell carcinomas to the thyroid. These include the presence of packed red blood cells within the follicle (glandular) lumens, the “water clear” nature of the cytoplasm (i.e. the cytoplasm lacks granularity), and a rich sinusoidal vascular pattern. The expansion of immunohistochemical probes has increased the role of immunohistochemistry as a diagnostic aid. In addition to metastatic renal cell carcinoma being negative for markers of follicular epithelial cells (thyroglobulin and TTF1), they are often positive for RCC and PAX-2.
In the present case, the absence of any history of renal cell carcinoma and the lack of unequivocal staining for RCC and PAX2 did not allow a definite histopathologic diagnosis. The clinicians were asked to perform imaging studies of the abdomen. An abdominal CT scan demonstrated a 3 cm mass in the right kidney.
Incorrect
Answer: Metastatic renal cell carcinoma
Histology: The thyroid shows multinodular adenomatoid hyperplasia, but one of the nodules is conspicuous for its composition of clear cells. The clear cells maintain a nested pattern of growth. There is a rich but delicate vascular network. The follicles are packed with red blood cells. The nuclei are small with condensed chromatin. Mitotic figures are not observed. Immunohistochemical studies were performed. The tumor cells are not immunoreactive for thyroglobulin, TTF1 or PAX2. An RCC immunostaining shows focal equivocal membrane staining.
Discussion: Prominent clear cell change can be encountered in various types of primary thyroid tumors. Cytoplasmic clearing is not uncommon for Hurthle cell neoplasm where and is believed to reflect mitochondrial swelling and degeneration. Clear cell change in follicular and papillary neoplasm usually reflects the cytoplasmic accumulation of glycogen. In the present case, the absence of staining for TTF1 and thyroglobulin raised the possibility of a tumor of non-follicular origin.
Metastatic involvement of the thyroid gland is not unusual, but it is usually seen in the context of widespread metastases. Metastatic involvement of the thyroid gland as a sentinel event in a patient with an occult primary tumor is a much rarer occurrence. In this situation, the most common primary tumor is renal cell carcinoma followed by colorectal carcinoma and malignant melanoma. In effect, metastatic renal cell carcinoma should always be included in the differential diagnosis of clear cell tumors involving the thyroid.
There are several morphologic features that are consistently present in metastatic renal cell carcinomas to the thyroid. These include the presence of packed red blood cells within the follicle (glandular) lumens, the “water clear” nature of the cytoplasm (i.e. the cytoplasm lacks granularity), and a rich sinusoidal vascular pattern. The expansion of immunohistochemical probes has increased the role of immunohistochemistry as a diagnostic aid. In addition to metastatic renal cell carcinoma being negative for markers of follicular epithelial cells (thyroglobulin and TTF1), they are often positive for RCC and PAX-2.
In the present case, the absence of any history of renal cell carcinoma and the lack of unequivocal staining for RCC and PAX2 did not allow a definite histopathologic diagnosis. The clinicians were asked to perform imaging studies of the abdomen. An abdominal CT scan demonstrated a 3 cm mass in the right kidney.
