A 34-year-old male patient with decreased libido, visual disturbance, and intermittent severe headache was referred to our Pituitary Center. Endocrinological evaluation at presentation revealed panhypopituitarism and hyperprolactinemia (Table 1). Despite appropriate hormone replacement therapy, his symptoms persisted. Ophthalmologic examination revealed decreased visual acuity, right temporal hemianopsia, and bilateral pallor of the optic disk. Pituitary magnetic resonance imaging (MRI) showed a thickening in the upper half of the pituitary stalk that extended to the right half of the chiasm (Figure 1a).
Serum levels of alpha-fetoprotein, β-human chorionic gonadotropin and angiotensin-converting enzyme were normal, and scrotal ultrasound findings were normal. Chest computed tomography (CT) and a tuberculin test ruled out sarcoidosis, tuberculosis, and lung cancer. Flow cytometry results of the cerebrospinal fluid were normal, and positron emission tomography-CT showed pathological hypermetabolism only in the right optic chiasm. Other diagnostic studies, including a skeletal examination to exclude histiocytosis, were normal.
An extended endoscopic transsphenoidal biopsy of the pituitary stalk lesion was performed. The lesion appeared as a yellowish, soft mass (Figure 1b). The postoperative course was uneventful. The pathological examination showed infiltration of lymphocytes, plasma cells, and histiocytes; thus, he was diagnosed as having primary lymphocytic hypophysitis (LH). High-dose methylprednisolone was administered immediately intravenously and then orally. There was no clinical response after 6 weeks of treatment and careful reevaluation of the biopsy identified two cell populations: larger tumor cells with atypical nuclei and small reactive lymphoid cells (Figure 1c). By demonstrating that these atypical cells were positive for Sal-like protein 4 (SALL4), a diagnosis of germinoma was made (Figure 1d). The patient received chemotherapy (bleomycin, etoposide and cisplatin). MRI revealed regression of the tumor after three courses.
Pituitary germinomas are difficult to distinguish from LH because of their similar clinical, radiological, and histopathologic findings. However, their distinction is important because of the different therapeutic approaches.1,2 In the case of a double lesion in the suprasellar and pineal regions, MRI may be pathognomonic for germinomas. However, pituitary stalk thickening may be seen radiologically in germinomas and LH.1,2 In addition, germinomas are highly immunogenic tumors and can cause a strong immune response that can attack the pituitary gland and lead to secondary hypophysitis.1,2 Therefore, a rich lymphocytic infiltrate is sometimes found in germinomas which is very challenging to identify.3,4
SALL4, a zinc finger transcription factor, is a novel stem cell tumor marker which essentially functions in maintaining pluripotency and self-renewal of embryonal stem cells.5 Therefore, SALL4 is strongly positive in all gonadal yolk sac tumors, seminomas/dysgerminomas, and embryonal carcinomas.5
Endoscopic transsphenoidal biopsy for the diagnosis of pituitary stalk lesions is safe and effective. Germinoma should be considered in LH cases that progress despite treatment, even if the initial pathological examination revealed a lymphocytic infiltrate. SALL4 may play a role in excluding LH.
Informed Consent: Informed consent was obtained from the patient.
Authorship Contributions: Concept- S.Ş., O.B., N.Ç., P.K., N.G.; Design- S.Ş., O.B., N.Ç., P.K., N.G.; Data Collection and Processing- S.Ş., O.B., N.Ç., P.K., N.G.; Analysis or Interpretation- S.Ş., O.B., N.Ç., P.K., N.G.; Literature Search- S.Ş., O.B., N.Ç., P.K., N.G.; Writing- S.Ş., O.B., N.Ç., P.K., N.G.
Conflict of Interest: No conflict of interest was declared by the authors.
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