Contributed by Bremer Pais I, MD1 *, Bernreuther C, MD3 *, Minnemann T, MD5, Saeger W, MD3, Hagel C, MD3, Iking-Konert C, MD4, Aberle J, MD1, Flitsch J, MD2
1Department of Endocrinology and Diabetology, 2Department of Neurosurgery, 3Institute of Neuropathology, 4Department of Nephrology and Rheumatology
University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 5amedes MVZ Hamburg GmbH, Mönckebergstraße 10 ,20095 Hamburg
*These authors contributed equally
CLINICAL SUMMARY
A 42 year old Caucasian male patient with known Hashimoto's thyroiditis presented the first time in 2010 with increased thirst and nocturia. An MRI of the pituitary gland in 2010 showed an enlarged pituitary stalk up to the infundibulum. Endocrinologically, there were normal levels for ACTH, LH, FSH, TSH, PRL, STH as well as for cortisol, testosterone and IGF-1. The clinical diagnosis of diabetes insipidus due to an autoinflammatory hypophysitis with a normal functioning anterior pituitary was made after excluding other reasons (e.g. sarcoidosis). A symptomatic treatment with desmopressin was initiated and regular follow-ups were held.
In early 2013, follow up revealed a loss of libido and sleep disturbances. An insufficiency of the gonadotropic axis was diagnosed. A MRI showed no progression of the known lesion, showing typical radiological signs seen in an autoimmune hypophysitis. The corticotrophic axis showed no insufficiency. Under testosterone treatment the symptoms resolved, however, 6 months later a corticotrophic insufficiency was diagnosed. Another MRI was performed (1/2014) and revealed further enlargement of the pituitary lesion as well as new periventricular lesions, worrisome for possible cerebral lymphoma. The clinical work-up included a lumbar puncture which excluded malignant cells as well as an MRI of the whole spine. Furthermore, the following lab results were repeated: IgG 4, ACE, CRP, β2-Mikroglobulin, pANCA, cANCA, β-HCG, AFP, PLAP and electrophoresis (ANA and ENA). None of these lab results showed pathological findings. A transsphenoidal biopsy (1/2014) revealed B-cell-rich inflammation without the diagnosis of a lymphoma or other malignancy.
After excluding a malignant process and other systemic inflammation process a high-dose treatment with corticosteroids (prednisone 1mg/kg) was initiated. Because of a progression in the follow-up MRI during treatment with corticosteroids, treatment was switched to methotrexate (15 mg/week, switched to 25 mg/week) and finally rituximab (Mabthera®) during the course of 12 months (1000 mg twice), leading to an improvement of clinical symptoms. Nevertheless, after the course of 12 months further progression of the tumor enhancements parasellar as well as periventricular were seen on MRI. A PET scan showed no pathological enhancements. Another lumbar puncture ruled out malignant cells within the CSF. A second transsphenoidal biopsy to exclude lymphoma was performed in the beginning of 2015 revealing the final surprising diagnosis 5 years after initial manifestation of the first symptoms.
NEUROIMAGING
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Initial coronal and sagittal contrast-enhanced MRI 2010 (Figs. 1a, 1b) showed enlargement of the pituitary stalk and no periventricular lesion. In 2014 (Figs. 1c, 1d), the MRI revealed a further enlargement intra- and suprasellar, as well as periventricular lesions. A year later (Figs. 1e, 1f), despite different therapeutic interventions for hypophysitis, the lesions had grown, leading to another biopsy.
PATHOLOGY
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Histological investigation of the specimen obtained in the first operation revealed fibrous tissue moderately infiltrated by lymphocytes (Fig. 1g). Immunohistochemical analysis identified most lymphocytes as CD3-positive T-cells (Fig. 1i) whereas CD20-positive B-cells were rarely detected (not shown). An immunohistochemical analysis with an antibody against placental alkaline phosphatase (PLAP) was performed. No PLAP-positive cells were detected (Fig 1k). An unspecific chronic inflammatory infiltrate was diagnosed. Histological investigation of the specimen obtained in the second operation revealed two different patterns. On the one hand, areas with dense lymphocytic infiltrates were seen. As in the specimen obtained in the first operation, CD3-positive T-cells prevailed (Fig. 1j). On the other hand, focally, islands of large epithelioid cells with big nuclei and prominent nucleoli were detected (Fig 1h). Remarkably, these islands contained only few lymphocytes. The large cells were positive for both PLAP (Fig 1l) and Oct 3/4 (not shown). What is your diagnosis?
International Society of Neuropathology