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Presented by Peter Illei, M.D. and prepared by Hillary Ross, M.D.
Case 1: 60 y.o. white female patient with enlarged nodular thyroid.
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1. Question
Week 416: Case 1
60 y.o. white female patient with enlarged nodular thyroid. FNA was positive for carcinoma with the differential diagnosis including papillary and medullary carcinoma. On gross exam, five well defined nodules were noted in both lobes and the isthmus that ranged from 0.5-1.5 cm. Four of these nodules showed identical histology (slide 1), whereas a 0.6 cm nodule showed different histology (slides 2-5).images/1alex/11302009case1image1.jpg
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images/1alex/11302009case1image5.jpgCorrect
Answer: Mixed medullary-papillary carcinoma in thyroid with multifocal papillary carcinoma
Histology: H&E sections of 4 of the 5 nodules show papillary carcinoma classic and follicular variants with typical nuclear features including intranuclear inclusions, nuclear grooves and nuclear clearing. The 0.6 cm mass in the right lobe shows different histology. It is composed of follicular structures that are lined by tumor cells that are similar to those seen in the papillary carcinomas. Infiltrating between these atypical follicular structures are sheets of small uniform tumor cells that have plasmacytoid appearance and small, round oval nuclei with speckled chromatin and no nucleoli. Scattered small lymphocytes are also noted. Immunostains demonstrate that the small plasmacytoid tumor cells are thyroglobulin negative, and calcitonin, chromogranin, and synaptophysin positive. The follicular structures on the other hand are positive for thyroglobulin and are negative for the three neuroendocrine markers. The staining pattern of these solid sheets of tumor cells is consistent with those of medullary carinoma while the atypical follicular structures are histologically and immunophenotypically consistent with papillary carcinoma, thus the diagnosis is a mixed medullary – papillary carcinoma of the thyroid.
Discussion: Mixed medullary and papillary carcinomas are tumors exhibiting morphological features of both tumor and are very rare tumors usually described as single case reports. In the reported series the mean age was 48 years. The male to female ratio was 1.3:1. Patients usually present with a cold nodule of the thyroid and mixed tumors have been shown to occur in patients with carcinomas caused by a germ line RET mutation. These mixed tumors usually present with metastatic disease. The metastases may exhibit a predominant pattern of either component. The majority of mixed medullary and papillary carcinomas are sporadic tumors, however, there are rare reported cases where these tumors are associated with MEN2 syndrome. The current case is unusual in as much as the mixed tumor is a small nodule in thyroid that contains multifocal papillary carcinoma of follicular and classic variants. Prognosis in this case that lacks evidence of metastatic disease is most likely be determined by the papillary carcinoma component.
Incorrect
Answer: Mixed medullary-papillary carcinoma in thyroid with multifocal papillary carcinoma
Histology: H&E sections of 4 of the 5 nodules show papillary carcinoma classic and follicular variants with typical nuclear features including intranuclear inclusions, nuclear grooves and nuclear clearing. The 0.6 cm mass in the right lobe shows different histology. It is composed of follicular structures that are lined by tumor cells that are similar to those seen in the papillary carcinomas. Infiltrating between these atypical follicular structures are sheets of small uniform tumor cells that have plasmacytoid appearance and small, round oval nuclei with speckled chromatin and no nucleoli. Scattered small lymphocytes are also noted. Immunostains demonstrate that the small plasmacytoid tumor cells are thyroglobulin negative, and calcitonin, chromogranin, and synaptophysin positive. The follicular structures on the other hand are positive for thyroglobulin and are negative for the three neuroendocrine markers. The staining pattern of these solid sheets of tumor cells is consistent with those of medullary carinoma while the atypical follicular structures are histologically and immunophenotypically consistent with papillary carcinoma, thus the diagnosis is a mixed medullary – papillary carcinoma of the thyroid.
Discussion: Mixed medullary and papillary carcinomas are tumors exhibiting morphological features of both tumor and are very rare tumors usually described as single case reports. In the reported series the mean age was 48 years. The male to female ratio was 1.3:1. Patients usually present with a cold nodule of the thyroid and mixed tumors have been shown to occur in patients with carcinomas caused by a germ line RET mutation. These mixed tumors usually present with metastatic disease. The metastases may exhibit a predominant pattern of either component. The majority of mixed medullary and papillary carcinomas are sporadic tumors, however, there are rare reported cases where these tumors are associated with MEN2 syndrome. The current case is unusual in as much as the mixed tumor is a small nodule in thyroid that contains multifocal papillary carcinoma of follicular and classic variants. Prognosis in this case that lacks evidence of metastatic disease is most likely be determined by the papillary carcinoma component.