Pediatric Oncologic Pathology
Moderators: Dr. Tony Bourne and Dr. Denis Benjamin
Case 1 -
Disseminated intravascular carcinomatosis, primary tumour never definitely
Dr. Marian Malone
Great Ormond Street Children's Hospital
London WC1N 3JH, UK
A 13 year-old girl of Turkish background who was previously well presented to her local hospital in
December 2005 with a 3 week history of severe, then moderate, left-sided headaches. These were
associated with ataxia, slurred speech and progressive left lower limb weakness and a one week history of
chorea. On examination, fundoscopy and cranial nerves were normal. She had choreiform movements,
dysarthria, ataxic gait, power 4/5 and hemireflexia on the left. Full blood count, erythrocyte
sedimentation rate C-reactive protein, anti-nuclear antibody, anti-streptolysin O titre and thyroid
function tests were normal. Magnetic resonance imaging showed multiple white matter lesions in the
cerebral hemispheres and infratentorially. A diagnosis of acute demyelinating encephalomyelitis (ADEM))
was made and she was treated with intravenous methylprednislone for 3 days followed by oral prednisolone.
Case 1 - Slide 1
In January 2006 she presented to Great Ormond Street with headaches, confusion and deterioration in
her speech. MRI showed new white matter lesions and a diagnosis of recurrence of ADEM was made. She was
again treated with i.v. methylprednisolone then oral prednisolone.
In March 2006, she complained of pain in her feet and lower legs, cold feet which had been progressing
over two months, four episodes of epistaxis over one week and headaches. In retrospect at her initial
presentation to her local hospital, she had a cold, pale pulseless right foot. She had no neurological
symptoms apart from residual word-finding difficulties Examination showed cool feet with pulses present
but difficult to feel. She had a new end-systolic murmur, maximum at the apex. She had systolic
hypertension with pressures of 130 and 120 in the right and left upper limbs respectively and 60 and 80
in the right and left lower limbs. Respiratory, abdominal and neurological examinations were normal.
Echocardiography showed a large vegetation on the mitral valve. She had a lymphopenia with a
relatively low platelet count, low fibrinogen and raised D-dimers with a normal coagulation screen. She
developed sustained hypertension and renal ultrasound scan showed a small left kidney which was poorly
functioning on DMSA scan. Rheumatoid factor and anti-nuclear antibody were weakly positive. Chest X-ray
was suggestive of hilar lymphadenopathy. Computerised tomography showed bilateral hilar lymphadenopathy,
a small right pleural effusion, focal consolidation in the right lower lobe and a 1cm nodule in the basal
segment of the right lower lobe. Quantiferon gold test for tuberculosis was positive and repeated
Mantoux tests were positive. Her mother was known to have had TB in 1998.A biopsy of lung and pleura and
sampling of the pleural effusion were carried out.
Cytological examination of the pleural effusion shows numerous reactive mesothelial cells admixed with
enormous signet ring-like cells, with eccentric pleomorphic nuclei and central vacuolar clearing of the
cytoplasm. The features are of a malignant pleural effusion.
The lung biopsy shows essentially normal architecture with no abnormal infiltration of airspaces and
no pneumonia.. However, numerous vessels are occluded by predominantly eccentric organising, apparent
thrombotic areas, affecting both veins and arteries while large artery branches contain intraluminal
clumps and clusters of pleomorphic cells with vesicular nuclei, prominent nucleoli and eosinophilic
cytoplasm. In places these clumps of large abnormal cells are admixed with organising thrombus with
lymphocytes and fibroblasts. An elastin stain shows eccentric intimal thickening of the pulmonary
Immunohistochemical staining shows the abnormal intravascular cells to strongly express pancytokeratin
(MNF 116). Staining for S 100, CD31, CD34, factor V1III- related antigen, CD 20 and CD 3 is negative.
The features are highly suggestive of a disseminated malignant intravascular epithelial tumour
The pleural biopsy shows marked dense fibroblastic proliferation with areas of hylalinosis,
macrophages, concentric abnormal calcifications and scattered signet ring-type cells. Immunostaining
shows a similar phenotype with the large pleomorphic cells showing strong cytokeratin positivity
The overall features are highly suggestive of disseminated malignancy, probable carcinoma,, likely
adenocarcinoma. It is not possible to determine with any degree of certainty on such material the origin
of the tumour, but breast carcinoma would be high on the list of differentials.
An entire body PET scan was carried out which was negative apart from a strongly avid nodule in the
basal segment of the right lower lobe. This was presumed to be the primary tumour.
She was transferred for palliative care to the Adolescent Oncology Unit at University College London
Hospital . Palliative chemotherapy was commenced with Cisplatin and Etoposide. A Doppler ultrasound scan
of the left leg showed no evidence of deep vein thrombosis. The differential blood pressure improved
over time. She developed anorexia and lethargy. In May 2006, she developed a sudden right hemiplegia
and aphasia. CT scan and MRI scan showed a "cerebrovascular accident". She became confused, and
developed a contralateral lack of movement. At no time did she suffer from respiratory symptoms. She
became anuric and died. Permission for autopsy was refused.
Acute demyelinating encephalomyelitis.
This is a rare condition of which there are no case reports in children. Adult cases have been
described as a para-neoplastic phenomenon associated with leukaemia, non-Hodgkin's lymphoma, seminoma
and adenocarcinoma of the lung. The pathology: is of sharply demarcated plaques of demyelination with
no associated malignant infiltration. There is perivascular lymphocytic cuffing. Diagnosis:is by MRI.
Acute multiple sclerosis should be excluded by searching for oligoclonal bands in CSF. Anti-neuronal
antibodies are negative (when reported).
An alternative explanation of the cerebral syndrome in the present case might be the presence of
intravascular tumour thrombi similar to those seen in the lung.
Differential diagnosis on the lung biopsy
80% of cases are reported in women. The age range is 12-61 years, mean 36 years. Clinical
presentation,is indolent and half the patients are asymptomatic. It may rarely present as thromboembolic
disease and may present as a solitary lung mass. The characteristic presentation is with multiple small
bilateral lung nodules. Histopathological examination shows lung nodules with central sclerotic
hypocellular zones and a cellular periphery. The centre can be calcified. Extensive lymphatic spread is
characteristic. The intercellular stroma consists of abundant hyaline matrix. Intracellular vacuoles
are common giving a signet- ring appearance. Tumour cells express CD31, CD34 and Factor VIII. Focal
cytokeratin expression is seen in 20-30% of cases.
This is an uncommon variant of large cell lymphoma. Most patients are middle-aged or elderly although
a congenital case has also been reported. Patients usually present with symptoms attributable to
involvement of the skin or CNS. CNS involvement usually presents as confusing bizarre and non-specific
neurological symptoms. Any organ or system can be involved. Histologically the key feature is filling
of the lumina of small and intermediate –sized blood vessels by non-cohesive large atypical mononuclear
cells. This can lead to multi-site infarction of many organs. Tumour cells usually possess round
nuclei, vesicular chromatin, multiple prominent nucleoli and a moderate rim of amphophilic cytoplasm.
Mitoses can often be seen. Tumour cells tend to be enmeshed in fibrin or platelet thrombi. Blood
vessels can become thrombosed. Immunhistochemically almost all cases are of B-cell lineage.
Disseminated melanoma is excluded in this case by negative immunostaining
for S 100.
It is regrettable that an autopsy was not performed. The complexity of presentation and the challenge
of establishing a diagnosis, even to the partial extent that was achieved, provide an exceptional
"teaching case" in which a definitive pathological diagnosis was never established. An autopsy would
have provided the best opportunity for doing so. In addition other ancillary questions might well have
Disseminated intravascular carcinomatosis, primary tumour never definitely