Contributed by Danijela Oštrić, MD1; Marija Todosijević, MD2; Anja Jeričević, MD1; Saša Šega Jazbec MD, PhD2; Mara Popović, MD, PhD1
1Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia,
2Neurology Clinic, University Medical Centre, Ljubljana, Slovenia.
A 36-year old right-handed female patient in the 21st week of pregnancy presented to the Neurology emergency department due to double vision, hypoesthesia on the right side of her face, headache, nausea and weight loss. The symptoms had started 4 months previously, when she was going through an IVF (in vitro fertilisation) procedure, with nausea and weight loss. She became pregnant a few weeks after the symptoms started. Neurological examination revealed right abducens nerve palsy and sensory loss in the area of the right maxillary and mandibular nerve. MRI, T1 weighted sequence, showed multiple lesions in the ventricular system, and one in the region of the right trigeminal nerve, which could have been metastases (Figures 1A and 1B - arrows pointed the tumors). The complete blood count showed mild anaemia. A lumbar puncture was performed, which revealed normal opening pressure, mild pleocytosis (6 leucocytes) and slightly elevated proteins. There were no malignant cells in the CSF, chest X-ray, and abdomen and breast ultrasound were unremarkable. The neurosurgeon suggested a biopsy of the lesions next to the trigeminal nerve but only after the delivery. The patient did not consider abortion. Her neurological condition slowly deteriorated and a caesarean section was performed in the 30th week of pregnancy, followed immediately by a biopsy of the lesion in the region of the right trigeminal nerve. She gave birth to a girl weighed 1400g. After the delivery, the patient's condition started to deteriorate at a more rapid pace, with a worsening of headache with vomiting, disorientation and gait instability. A head CT scan showed obstructive hydrocephalus and open ventricular drainage was performed, after which the headaches subsided. She started treatment with radiotherapy. Seven weeks after delivery and 10 months after the beginning of her symptoms, she became unconscious with unreactive pupils and was admitted to the intensive care unit. A CT scan showed hematocephalus and obstructive hydrocephalus. She died the same day.
Small pieces of tissue from the right Gasser's ganglion, approximately 1 cubic centimeter, were sent for examination. Microscopically, the ganglion was heavily infiltrated by tumor cells with abundant slightly granular cytoplasm and moderately polymorphic nuclei, occasionally with nuclear grooves, and distinct nucleoli. Mitotic figures were present (Figures 2A - arrows pointed the ganglion cells, 2B). Immunohistochemical workup came out as follows: tumor cells were negative for epithelial (CK7, CK20, AE1/AE3, EMA), melanoma (melan A, HMB45, S-100), lymphomas markers (CD3,CD20,CD79a,CD138), markers of Langerhans cells (CD1A, langerin), neuroepithelial/neuroendocrine markers (chromogranin, Syn38,CD56, and GFAP,), germ cells markers (OCT4 in SALL4), markers for the tumors of urogenital tract (PAX8) and markers for estrogen and progesterone receptors, but were strongly positive for CD68 (Figure 2C - arrows pointed at the ganglion cells), CD4, CD45 and CD45RO. The Ki-67 proliferation index was 40%. Additionally, two more immunoreactions, CD163 and PU1, were done in another laboratory and came out positive.
POST MORTEM FINDINGS
The formalin fixed brain weighed 1490g. Coronal sections showed scattered grayish tumors up to 2cm in diameter, located in the body of both lateral ventricles attached to the ependymal surface. Smaller tumors were present in the fourth ventricle, infiltrating the cerebellum and medulla (Figures 3A and 3B, respectively). The aqueduct and fourth ventricle were filled with blood due to secondary hemorrhages in the brainstem. The spinal cord was macroscopically unremarkable but, on microscopic examination, the spinal roots were infiltrated by tumor cells, which focally entered the spinal cord parenchyma as well as subarachnoid space, which was also infiltrated by tumor cells intracranially. The feature of erythrophagocytosis by tumor cells was frequently evident (Figures 3C and 4A). The right oculomotor nerve was thicker than the left one due to tumor cell infiltration (Figure 3D). Severe tumor cell infiltration was present in the reminder of the intracranial part of the left trigeminal nerve, as well. Extra axial spread of the tumor cells was evident only in the liver, with disseminated tumor cells creating only two macroscopically visible foci, and pituitary gland (Figures 4A and 4B, respectively). All tumors described showed the same microscopic features as those in the biopsy specimen. What is the diagnosis?