A 28 YEAR OLD LADY WITH A PITUITARY MASS

CLINICAL HISTORY

A 28‐year‐old woman presented with amenorrhea and blurred vision for 3 years and was admitted to our hospital for further evaluation. MRI of the brain was performed and the coronal T2 weighted image revealed a well defined, high signal mass 26 × 22.5 × 21 mm, in the left anterior lobe of the pituitary gland. The pituitary stalk was elevated (Figure 1). Serum prolactin level was 40.4 ng/ml (normal range: 3.0–20.0 ng/ml). The other results were within normal range. The preoperative survey revealed no evidence of other tumor in the body. The patient underwent transsphenoidal adenomectomy.

Figure 1.

NEUROPATHOLOGICAL FINDING

Microscopically, the tumor was composed of clusters of large bizarre and pleomorphic tumor cells, which displayed large vesicular nuclei, prominent nucleoli, smudgy chromatin and abundant pale eosinophilic cytoplasm. The tumor cells were arranged in a diffuse sheet‐like growth pattern. In addition, there were heavy lymphocytic infiltrations and formation of germinal centers in the background. Mitotic figures were hard to find (Figure 2 and Figure 3). Immunostaining of the tumor demonstrated strong positive staining with synaptophysin (Figure 4), chromogranin and only a small number of tumor cells reactive for TSH. The other stains for pituitary hormones, including PRL, GH, ACTH, and FSH; and the germ cell‐related immunostains were all negative. The Ki‐67/MIB‐1 labeling index was about 10–20%, while the p53 staining was negative. The infiltrative lymphocytes were immunoreactive for CD20 (Figure 5) and CD3 (Figure 6) markers.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

DIAGNOSIS

Atypical pituitary adenoma with prominent lymphocytic infiltration and germinal centers.

DISCUSSION

Pituitary neoplasms are the third most common intracranial tumor after meningiomas and gliomas. Typically pituitary adenomas are composed of cells with uniform round nuclei, delicate stippled chromatin, inconspicuous nucleoli and a moderate amount of cytoplasm. Mitoses are uncommon and the Ki‐67 (MIB‐1) labeling indices are usually less than 3%. Based on the 2004 edition of the WHO classification of tumors of endocrine organs, some pituitary tumors with features of atypical morphology, elevation of mitotic figures and a Ki‐67 labeling index greater than 3%, as well as extensive diffuse nuclear staining of p53, are considered “atypical adenoma”(3). In this case, large pleomorphic tumor cells with prominent nucleoli were observed, as well as elevated Ki‐67 labeling index to 15%. The diagnosis of pituitary carcinoma requires identification of distant metastasis. Mitotic figures, proliferating cell nuclear antigen (PCNA), Ki‐67/MIB‐1, and anti‐apoptotic Bcl‐2 have demonstrated no consistent correlation with tumor behavior (1). The DNA topoisomerase II alpha, a marker for cellular proliferation, as well as Galectin‐3 (a marker for cellular differentiation and angiogenesis) have also been studied, but so far none have correlated with the behavior of atypical adenomas 5, 6.

Lymphocytic infiltration is a rare finding in pituitary adenomas as shown by Heshmati et al who found lymphocytic infiltration in 2.9% of 1400 cases reviewed. The frequency was not statistically different in major categories of secreting adenomas. However, unlike our case, no germinal centers were ever found and the lymphocytes were almost exclusively T cells (4). In the present case, the lymphocytes infiltration was either perivascular or in interstitial areas with frequent germinal center formation. The immunostaining for CD20 highlights nodular aggregation of B‐cells that correspond to the germinal centers, while the CD3 highlights the T cells in the interfollicular area.

Tumors occurring in the pituitary stalk with prominent lymphocytic infiltration include pituitary adenomas, germinomas, and lymphocytic hypophysitis. Germinomas are composed of uniform large germ cells with prominent nucleoli and usually a dense lymphocytic infiltrate. The germinoma tumor cells often stain positive for either Placental alkaline phosphate (PLAP) or c‐kit, or both. Serum and CSF assays for α‐fetoprotein and placental alkaline phosphatase are also helpful in preoperative diagnosis of a germ cell tumor. Lymphocytic hypophysitis is characterized by infiltration of the anterior pituitary gland by lymphocytes and plasma cells with destruction of the gland and eventual fibrosis. Germinal centers are occasionally identified. This condition is almost exclusively encountered in postpartum women (2). In summary, we have reported an atypical pituitary adenoma with prominent lymphocytic infiltration and germinal centers. The significance of lymphocytic infiltration in pituitary adenoma remains to be established.

ABSTRACT

We present a case of an atypical pituitary adenoma with prominent lymphocyte infiltration and germinal center formation. Histologically, the tumor revealed clusters of large pleomorphic cells with vesicular nuclei, prominent nucleoli, smudgy chromatin, and abundant eosinophilic cytoplasm. There was heavy lymphocyte infiltration and prominent germinal center formation. Mitoses were rare, and the Ki‐67 index was 15%. The lymphocytes were composed of both CD3‐positive T lymphocytes and CD20‐positive B‐cells. The diagnosis was atypical pituitary adenoma. Germinal centers have not previously been reported in these tumors. It is important to correlate histology and immunohistochemistry to differentiate this adenoma from other pituitary lesions with prominent lymphocyte infiltration, such as germinoma and lymphocytic hypophysitis.