Answer: Metastatic pituitary carcinoma

Histology: A lymph node is partially replaced by cords of cells in a collagenized background. The tumor cells have a plasmacytoid appearance with eccentrically placed nuclei and pink cytoplasm. The nuclei are round, uniform, and have a stippled chromatin pattern. The tumor does not exhibit high grade cytologic features, and tumor necrosis is not appreciated. An immunohistochemical pattern was performed. The tumor cells were immunoreactive for AE1:AE3 (perinuclear do pattern), chromogranin, and human growth hormone; and they were not immunoreactive for estrogen, progesterone, calcitonin, prolactin or ACTH.

Discussion: Pituitary carcinomas are exceptionally rare. The hallmark diagnostic feature of malignancy is metastatic spread. There are no histopathologic features that reliably predict a malignant clinical course. Two patterns of metastastatic spread are recognized: non-contiguous implantation within the central nervous system, and spread outside of the CNS to some systemic site. Most pituitary carcinomas are functional, the majority secreting either ACTH or prolactin.

Given the shortage of growth hormone secreting pituitary carcinomas, they do not commonly enter the differential diagnosis when dealing with cervical lymph node metastases. Once the neuroendocrine nature of a metastatic implant in the neck is established, the differential diagnosis more routinely includes a metastasis from the thyroid (metastatic medullary carcinoma) or the larynx (metastatic moderately differentiated neuroendocrine carcinoma). Establishing the correct diagnosis requires careful correlation of the clinical and serologic findings. We learned that this particular patient had a growth hormone producing pituitary adenoma removed in the early 1980s, and that she had persistently elevated levels growth hormone levels that were attributed to persistent disease at the base of the brain. Serum calcitonin levels were normal, and she had no history of breast cancer. As most of the metastases are functional, immunohistochemistry can also be useful in establishing the diagnosis. Interestingly, this tumor was not only strongly human growth hormone positive, but the perinuclear dot pattern of cytokeratin staining is well recognized for a subset of HG-secreting pituitary neoplasms.