Pituitary and systemic autoimmunity in a case of intrasellar germinoma

Abstract

Germinomas arising in the sella turcica are difficult to differentiate from autoimmune hypophysitis because of similar clinical and pathological features. This differentiation, nevertheless, is critical for patient care due to different treatments of the two diseases. We report the case of an 11-year-old girl who presented with diabetes insipidus and growth retardation, and was found to have an intra- and supra-sellar mass. Initial examination of the pituitary biopsy showed diffuse lymphocytic infiltration of the adenohypophysis and absent placental alkaline phosphatase expression, leading to a diagnosis of hypophysitis and glucocorticoid treatment. Because of the lack of clinical and radiological response, the pituitary specimen was re-examined, revealing this time the presence of scattered c-kit and Oct4 positive germinoma cells. The revised diagnosis prompted the initiation of radiotherapy, which induced disappearance of the pituitary mass. Immunological studies showed that the patient's serum recognized antigens expressed by the patient's own germinoma cells, as well as pituitary antigens like growth hormone and systemic antigens like the Sjögren syndrome antigen B and alpha-enolase. The study first reports the presence of pituitary and systemic antibodies in a patient with intrasellar germinoma, and reminds us that diffuse lymphocytic infiltration of the pituitary gland and pituitary antibodies does not always indicate a diagnosis of autoimmune hypophysitis.

Fig. 1

Cranial MRI images. Sagittal T1 post-contrast images showing the sellar and supra-sellar mass at diagnosis (a), after glucocorticoid treatment (b), and after radiotherapy (c)

Fig. 2

Pituitary histopathology. a Frozen section of the pituitary biopsy showing a marked mononuclear cell infiltration of the anterior pituitary. b A pan-B cell staining (CD79) shows the heavy infiltrate of B lymphocytes (similar pattern was obtained using CD3 for T lymphocytes, data not shown). c H&E staining of the formalin-fixed pituitary biopsy, showing a few germinoma cells (inset). d c-Kit staining clearly highlights the germinoma cells

Fig. 3

2-D gel electrophoresis and immunoblotting. Panels a and b represent the Coomassie blue staining of 2-D gels prepared from human pituitary cytosolic proteins, in the pH range from 5 to 6 (a) and 6 to 7 (b). c,d Show the corresponding immunoblotting, after the gels were transferred to nitrocellulose membranes and probed using the serum from the germinoma patient

Fig. 4

1-D gel electrophoresis and immunoblotting. The gel showed that the germinoma patient’s serum recognized La recombinant protein (added in decreasing concentration from lane 3 to 5). Lane 1 is the positive control using the serum from a lupus patient known to have La autoantibodies

Fig. 5

Immunohistochemistry performed using the patient’s own pituitary biopsy and serum. The serum contains antibodies that recognize the large germinoma tumor cells (arrow), among the heavy lympho-plasmacytic infiltrate