RN Auer, FA Magee, YX Wu
University of Saskatchewan, Saskatoon, Canada
A 2-year-old first nations girl presented with respiratory failure and generalized lymphadenopathy. Birth and delivery had been normal, and were followed by a normal infancy. There was no evidence of immunodeficiency, but at age 9 months pus drainage from both ears led to a brain CT that showed very mild prominence to the basal cisterns as well as the subarachnoid space predominantly over the frontal lobes, in keeping with benign macrocephaly of infancy. The brain parenchyma was unremarkable. Fluid filled the majority of the right and left middle ear and mastoid air cells with obliteration of the external auditory canal and punctate foci of gas present. Superficial to the right side of the occipital bone was a 3.5×0.9×3.7 cm area of approximately 20 HU (greater than simple fluid) of uncertain etiology, felt to possibly represent a resolving hematoma or infected collection. A cervical lymph node was biopsied and showed no evidence of a Hodgkin or non-Hodgkin lymphoma. She developed eczema. Age 2 she was admitted for asthma with respiratory failure, eczema, cervico-thoracic lymphadenopathy. MRI of the pelvis and buttocks revealed findings that had progressed, showing extensive subcutaneous edema, hepatosplenomegaly, mild nephromegaly, extensive multistation adenopathy including retroperitoneal, mesenteric, pelvic and inguinal as well as thoracic and cervical adenopathy. There was conglomerate mass surrounding vessels in the abdomen including mesenteric and aortic branch vessels. Moderate ascites was centered predominantly in the lower abdomen. Dense consolidation was seen in the right lung. The constellation of imaging features was deemed non-specific, with infection, inflammation, and neoplasm all possible and it was concluded that “Pathologic diagnosis will be important”. A central venous line, endotracheal intubation, and a feeding tube were placed. Imaging further revealed small left and right pleural effusions, and left lower lobe retrocardiac consolidation. A diagnosis of sepsis and lymphoma were both queried. She continued to deteriorate. Neurologic symptoms appeared. Pulmonary function decreased. She died at the age of 2 years, 8 months. Permission for an unrestricted autopsy was granted.
Neuropathologic examination revealed a 1000 g brain after fixation, with no external abnormalities and no gross lesions visible on coronal sectioning. Brain sampling included 20 blocks, and microscopic disease was seen in every section.
Material submitted: one representative H&E stained section of brain.
Questions: Diagnosis? What stains would you like to establish the diagnosis?
A Montazeri1, BJ Schmidt2, P Dhaliwal3, S Kakumanu4, S Krawitz5
1Max Rady College of Medicine; 2Section of Neurology, Department of Medicine; 3Section of Neurosurgery; 4Department of Radiology; 5Department of Pathology; all at University of Manitoba
This 51-year-old man presented with a four week history of left lower limb and abdomen paresthesia and right lower limb weakness. His history was unremarkable apart from tuberculosis 20 years ago. Physical examination revealed increased tone and decreased strength in the right lower limb, an extensor plantar response on the right, and decreased pinprick sensation to the T4 level on the left.
MR imaging showed an expansile 2.5 cm enhancing lesion in the right cervical hemicord, centered at C7. MRI of the brain was normal. CT of chest, abdomen, and pelvis, and scrotal sonogram were normal at the time of presentation and 18 months later at the time of biopsy. MR angiography of the neck and intracranial vessels, CBC, biochemistry, immunology, and CSF were normal.
He did not respond to a trial of steroids. Symptoms remained stable for 12 months at which time he noted numbness involving his right thorax. Serial MRIs revealed no change until 11 months after presentation at which time a new enhancing nodule (5 mm) appeared at the C3 cord level and there was slight progression of the original C7 lesion. The patient declined biopsy until six months later, during which time he showed slight further clinical progression.
Materials submitted: one digitally scanned H&E slide
AF Gao1,2, M Abdollahi1, DG Munoz1,2
1Dept. of Laboratory Medicine, St. Michael’s Hospital and 2Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
A 59-year-old man presented with a 4-week history of headaches, diplopia, and ataxia. This was accompanied by mild lower extremity weakness, urinary retention, and constipation. Physical examination revealed disturbances in eye movements, bilateral leg weakness with spastic hyperreflexia, dysmetria, and truncal ataxia. Neuroimaging showed T2/FLAIR hyperintensities in the bilateral thalami, right cerebellar hemisphere, and vermis with diffuse leptomeningeal enhancement of the brainstem, spinal cord, and cauda equina.
Multiple lumbar punctures were significant for elevated opening pressure (>30mmHg) and markedly elevated protein (>20g/L), but were otherwise unrevealing. Extensive investigations for infectious, rheumatologic, autoimmune, and paraneoplastic etiologies were negative. CT scan of the chest/abdomen/pelvis and testicular ultrasound were unremarkable. A biopsy of the frontal lobe showed a mild leptomeningeal histiocytic infiltrate, which was clinically interpreted as being consistent with an inflammatory process such as neurosarcoidosis.
The patient was treated with immunosuppressive therapy but showed minimal response despite progressive escalation of immunosuppression over multiple hospital admissions. During his final admission, 6 months after presentation, the patient continued to deteriorate and ultimately became comatose with radiologic findings of herniation and global hypoxic-ischemic injury. An autopsy was performed.
Materials Submitted: Representative MRI images from initial presentation, 2 representative H&E-stained sections
Questions: Diagnosis? Molecular alteration?
KD Langdon1, H Lin2, C Hawkins3 and Q Zhang1
1Department of Pathology and Laboratory Medicine, LHSC, Western University, London, Ontario; 2Division of Molecular Diagnostics, Pathology and Laboratory Medicine, LHSC; 3Division of Pathology, Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University of Toronto, Canada
This patient is a 2-year-old girl born at term following an unremarkable pregnancy. Her APGARs were 8 and 10 at 1 and 5 minutes, respectively. She was diagnosed with esotropia requiring operative management at 4 months. Her development is normal.
There is a family history of a paternal grandfather with a vestibular schwannoma, resected at the age of 70. There is no other history of brain tumours or malignancy.
She presented with a one month history of nausea, vomiting and unstable gait. There were no visual changes, abnormal movements or seizures.
Initial CT head revealed a hyperdense left posterior fossa lesion measuring 48 x 51 x 33 mm causing significant mass effect and effacing the fourth ventricle. MRI head further characterized the lesion as most likely intra-axial, mainly solid mass with small peripheral cysts causing distortion of the brainstem structures and hydrocephalus. There were heterogeneous hyperintensities on T2, hypointense on T1 and mild heterogeneous enhancement following gadolinium administration. Spinal imaging was unremarkable.
She underwent a suboccipital craniotomy for gross total lesion resection. The following was submitted for microscopic evaluation.
Materials Submitted: one representative H&E stained section
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL
This 58 year old man re-presented to an outside facility with recurrent back pain.
10 years earlier he developed seminoma of the left testicle (T1 N0 M0); he subsequently underwent right orchiectomy. Family history was negative for cancer syndromes. An incidental radiolucent 1.8 cm T8 vertebral body lesion was not hypermetabolic on PET/CT. He was well for 2 years until developing back pain, attributed to a compression fracture of T8. Surgical management revealed a solitary plasmacytoma (IgG kappa). He was left with a kyphotic deformity and persistent pain but was neurologically intact. He received local intent-to-cure radiotherapy but maintained a persistent M spike. He was stable until a positive bone marrow biopsy (iliac crest) 7 years after initial presentation. PET scanning revealed multiple lytic lesions, and he then entered a clinical trial of daratumumab (anti-CD38 mAB) added to standard chemotherapy. He also underwent autologous bone marrow transplantation.
He was stable until a few months before the most recent presentation when he sustained a back injury, resulting in mid-thoracic radicular pain. He was neurologically intact apart from stable peripheral neuropathy attributed to prior chemotherapy. Imaging revealed a T7-9 paravertebral enhancing mass with involvement of the T9 vertebral body and spinal cord compression. Biopsy and decompression were undertaken. Subsequent bone marrow biopsy was clear of myeloma, and PET/CT was negative for additional hypermetabolic lesions.
Material submitted: one representative H&E (scanned) section
Questions: Diagnosis? pathogenesis?
M Abdollahi1, DG Munoz MD1,2,3
1Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada, 2Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada, 3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
The patient was a 47-year-old female with a 10-year history of neuropsychological issues including psychotic episodes (paranoia, hallucinations, ideas of reference), depression, anxiety, panic attacks and restless leg syndrome. Initially there were episodes of aphasia, confusion and intense headaches lasting for several hours. She would return to baseline after each incident but in 2011 following several episodes of full body tremors and decreased level of consciousness, she did not recover to physical or cognitive baseline. On one occasion, she was hospitalized with right-sided paresis, speech difficulty and confusion which was diagnosed as hemiplegic migraine. Extensive laboratory work-up did not yield any abnormalities other than mild elevation of protein levels in the cerebrospinal fluid (0.65 g/L).
Progression of symptoms resulted in inability to take care of herself and she had to be moved to a nursing home in 2012.
Serial imaging showed progressive cerebral atrophy, brainstem calcifications and central hypodense areas in the corpus callosum.
In November 2017 she was hospitalized with status epilepticus. She was not able to swallow, had significant respiratory symptoms and passed away on November 21st, 2017. An autopsy was carried out upon the family’s request.
Questions Diagnosis? Ancillary tests?
R Van Ommeren1, GH Jansen2, LN Hazrati1
1Division of Pathology, The Hospital for Sick Children, Toronto, Canada, 2Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada
A previously healthy 15-year old girl presented with progressive neurologic deterioration. Perinatal, developmental, past medical, and family histories were unremarkable. Early months of her condition were characterized by headaches, confusion, behavioural disturbances, hallucinations, sleep disturbances, memory loss, and reduced cognitive capacity. Neurological examination identified pressured speech, confusion, and deficits in attention, recall, and concentration. Baseline bloodwork was initially found to be unremarkable. Initial MRI showed generalized volume loss, and EEG showed severe bilateral slowing with a background rhythm and no evidence of epileptiform activity. The patient was referred for extensive infectious, vasculitic, and genetic work-up, all of which returned normal. She continued to worsen neurologically, with progressive onset of choreoathetosis, myoclonus, tonic-clonic and generalized seizures, and dementia. Subsequent imaging continued to show progressive diffuse volume loss. She eventually lost all speech capacity, and became unresponsive to stimuli by age 21, and succumbed at 25 years of age. A neuropathological examination was performed post-mortem.
Materials submitted: Representative H&E stained sections:
KD Langdon1, E ZapataAldana2, S Al-Mobarak2, C Campbell2, RR Hammond1
1Department of Pathology and Laboratory Medicine, LHSC, Western University, London, Ontario; 2Division of Pediatric Neurology, LHSC, Western University, London, Ontario
This patient is a 2-year-old boy born at term following an unremarkable pregnancy. At three months the parents noticed motor delay and, in certain positions, he had abnormal ‘jerking’ of his legs lasting ~5 seconds. He was seen by a pediatrician who reassured the parents that this was likely within normal limits of child development.
His condition deteriorated and at 16 months he was seen by a neurologist. On examination, he was unable to sit and did not have head control. He had low axial tone, diffusely reduced muscle bulk and pectus carinatum. The neurologist noted mild bilateral ptosis with normal eye and facial movements and no tongue fasciculation. Muscle strength was low throughout, but anti-gravity movements were evident. There was bilateral ankle clonus and bilateral hip abductor contractures. He was able to reach and had normal fine motor skills for his age.
At 23 months he had generalized low tone and muscle bulk. His thorax was short with extremely limited movement of the thoracolumbar spine. There was proximal weakness but where possible, was able to grab objects easily. There were now contractures of the hip flexors, abductors and adductors. His social and verbal development were normal.
He was admitted for adenoidectomy and underwent a muscle biopsy at that time. The following was submitted for microscopic evaluation.
Material submitted: one representative HPS stained section.
Questions: Differential diagnoses? Possible genetic mutations?