Oncology imaging: Diagnosis
1 Lake Smit and Partners, Durban, South Africa
2
Oncologist,
Durban, South Africa
We congratulate Drs Vanesha Naidu of King
Edward VIII Hospital, Durban, and Ayesha Mitha of Inkosi Albert
Luthuli Central Hospital, Durban, for their excellent diagnoses,
for which they share the award of R1 000 from the RSSA. Drs
Misser et al. elaborate below on
the images and findings. Please refer to pages 74 - 76 of the
June 2013 issue of the SAJR
(http://www.sajr.org.za/index.php/sajr/article/view/890/724) for
the presenting details (recent onset personality change,
depression and cognitive impairment) and the investigative
images.
Diagnosis
Imaging and findings
The current imaging undertaken for new-onset neurological symptoms is superimposed on a background of long-standing neoplastic disease. The clinical context in this patient is therefore of great importance to the diagnosis.
The brain MR images (Figs 1 - 3) demonstrate abnormal increased T2-weighted and flair hyperintensity in the medial temporal lobes, particularly on the left side, including the hippocampal formation and amygdala. There is corresponding subtle T1-weighted shortening in the left limbic structures but no significant post-gadolinium enhancement (Fig. 4), which favours an inflammatory/encephalitic process over neoplastic/metastatic disease.
His prior imaging studies (Figs 5 - 13) show extensive intra-abdominal lymphadenopathy, predominantly involving retroperitoneal (para-aortic, interaortocaval, paracaval) and juxtarenal groups. All nodal masses demonstrate restricted diffusion on the diffusion B1000 study (Fig. 10) and corresponding ADC shortening (Fig. 11).
There is evidence for metastatic disease including:
• right lung base nodular parenchymal deposit (Fig. 8)
• left pleural effusion and sub-pleural nodular metastasis (Fig. 12)
• bony metastases to the thoracolumbar vertebral bodies D11, L1 and L2 (Figs 5 - 7)
• hepatic
parenchymal lesions in both lobes (Figs 9 - 13).
Hepatocyte-specific contrast MRI shows the metastatic lesions as hypo-intense non-enhancing foci on a background of homogenously enhancing liver parenchyma. Most of them demonstrate restricted diffusion as well. Note the low signal ovoid focus within the lumen of the contrast opacified IVC (Fig. 13) owing to intracaval tumour invasion.
The combination of distant haematogenous and regional nodal metastases, also seen on the sagittal lumbar spine MRI (Figs 5 - 7), in a young male patient is most probably due to a testicular germ cell tumour. Lymphoma is a plausible differential diagnosis. The current neurological presentation is due to paraneoplastic limbic encephalitis.
The patient was treated with salvage
chemotherapy and, on follow-up imaging, the nodal masses were
noted to be much smaller, the hepatic metastases had cleared
completely, the limbic encephalitis changes had resolved, and
there was normalisation of tumour markers. At relook laparotomy,
the remaining para-aortic nodes were noted to be irresectable.
His future management will depend on monitoring of the tumour
markers. If there is a rapid elevation in levels, then
chemotherapy will be re-introduced. If there is a gradual
increase, localised small fields of radiotherapy will be applied
to the residual metastatic nodes.
Discussion
Paraneoplastic syndromes are rarely encountered in clinical practice. The relationship between tumours and distant organ symptomatology not attributable to direct tumour effect or metastasis has been described over a century ago. These syndromes represent a distant manifestation of neoplasia on an auto-immune basis. The paramalignant syndromes are divided into paraneoplastic neurological syndromes (PNS) and non-neurological syndromes. Here we will focus on PNS as it is relevant to the patient presented. The pathophysiology of PNS is complex (Fig. 1 in this diagnosis).
During early neoplasm development, apoptotic
cells become phagocytosed by dendritic cells and are transported
to lymph node stations. There, the dendritic cells induce a
cascade of humoral and cell-mediated responses including the
activation of T-lymphocytes and B-cells. The B-cells mature into
plasma cells and produce antibodies against a tumour-specific
antigen in an attempt to destroy it. There are, however,
instances where the cytotoxic T-lymphocytes and antibodies
produced by the body cross-react with normal tissues and destroy
them. Depending on the auto-antibody formed, immune
cross-reactivity occurs with destruction of normal tissue, and
symptoms relevant to that organ system will manifest. In PNS,
one of the components of the nervous system (Table 1) will be
involved owing to immune cross-reactivity by the produced
onco-neural antibodies. Fig. 1 describes the combined
auto-immune response resulting in destruction of neuromuscular
junction in the Lambert-Eaton myaesthenic syndrome. The same
principle applies to the other PNS subtypes.
An increasing number of onconeural antibodies have been identified in patients with PNS, including anti-Hu, anti-CV2, anti-Ma and anti-Ta (Ma2), among several others.1 Anti-Ta (Ma2) typically occurs in young men with testicular germ cell tumours (including extragonadal sites). Paraneoplastic limbic encephalitis (PNLE) was first described by Corsellis et al.2 in 1968. Patients with PNLE may present with subacute personality change, major depression, irritability, amnesia and convulsions. Some patients can progress to dementia.
The
diagnosis of PNLE depends on several related criteria, as
outlined in Table 2. Radiological imaging by MRI has
become an integral component in making this profound clinical
diagnosis. On flair and T2-weighted imaging, abnormal
shortening resulting in hyperintensity is usually documented
in the temporobasal regions, especially the limbic structures
including the hippocampus and amygdala. The main differential
diagnosis for these MRI changes is herpes simplex
encephalitis, the presentation of which is more acute. In many
instances, the flair sequence may be the only contributory
sequence depicting the medial temporal lobe abnormality.
Gultekin et al.3 showed absence of T2-weighted
abnormalities in 43% of their series of patients.
Corresponding T1-weighted low signal may be seen and
post-gadolinium enhancement is generally absent. Isolated
cases demonstrating post-contrast T1-weighted enhancement of
the limbic structures have been documented. In clinical
practice, the radiologist is usually the first to raise the
alarm that a paraneoplastic phenomenon is suspected, and
correlation with other criteria for PNLE follows.
Generally, these patients respond well to
immunotherapy and treatment of the underlying malignancy.1 Follow-up
imaging to document clearing of the medial temporal lobe
abnormality is recommended. The radiologist therefore plays a
pivotal role in the diagnosis and follow-up of these patients.
1. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. New Engl J Med 2003;349:1543-1554. [http://dx.doi.org/10.1056/NEJMra023009]
2. Corsellis JA, Goldberg GJ, Norton AR. “Limbic Encephalitis” and its association with carcinoma. Brain 1968;91(3):481-496. [http://dx.doi.org/10.1093/brain/91.3.481]
3. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Damau J. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481-1494. [http://dx.doi.org/10.1093/brain/123.7.1481]
S Afr J Rad 2013;17(3):117-118. DOI:10.7196/SAJR.936