|Year : 2013 | Volume
| Issue : 1 | Page : 141-144
Mortui vivos docent - the dead teach the living: 18-flurodeoxyglocose positron emission tomography-computed tomography findings in a case of intravascular B cell lymphoma
Prathamesh V Joshi1, Vikram R Lele1, Imran Shaikh2
1 Department of Nuclear Medicine and PET-CT, Jaslok Hospital and Research Centre, Worli, Mumbai, India
2 Department of Oncology, Jaslok Hospital and Research Centre, Worli, Mumbai, India
|Date of Web Publication||10-Apr-2013|
Prathamesh V Joshi
Department of Nuclear Medicine and PET-CT, Jaslok Hospital and Research Centre, Worli, Mumbai
Source of Support: None, Conflict of Interest: None
Intravascular large B-cell lymphoma is a rare and aggressive variant of diffuse large B-cell non-Hodgkin's lymphoma. Its atypical presentation often delays the diagnosis and due to its aggressive behavior, the diagnosis is made post-mortem in half of the cases. We present FDG PET/CT findings in a case of IVLCL. In our case, the report of the patient's bone marrow biopsy after death of the patient revealed the presence of IVLCL. After availability of final diagnosis, we reviewed the literature and a better explanation of the FDG PET/CT findings could be obtained. We describe this case, to call for heightened awareness in physicians for the rare but possible diagnosis of IVCLL, particularly in an elderly patient who presents with fever of unknown origin and demonstrates similar FDG PET/CT findings. Considering the characteristic scan findings described in our patient and other cases in literature, FDG PET/CT can be used in suspected cases of IVLCL for early diagnosis of this rapidly fatal malignancy.
Keywords: FDG PET/CT, fever of unknown origin, Intravascular large B-cell lymphoma, non-Hodgkin′s lymphoma
|How to cite this article:|
Joshi PV, Lele VR, Shaikh I. Mortui vivos docent - the dead teach the living: 18-flurodeoxyglocose positron emission tomography-computed tomography findings in a case of intravascular B cell lymphoma. J Can Res Ther 2013;9:141-4
|How to cite this URL:|
Joshi PV, Lele VR, Shaikh I. Mortui vivos docent - the dead teach the living: 18-flurodeoxyglocose positron emission tomography-computed tomography findings in a case of intravascular B cell lymphoma. J Can Res Ther [serial online] 2013 [cited 2020 May 28];9:141-4. Available from: http://www.cancerjournal.net/text.asp?2013/9/1/141/110377
| > Introduction|| |
Intravascular large B-cell lymphoma (IVLCL) is a rare and aggressive variant of diffuse large B-cell non-Hodgkin's lymphoma (NHL). The current World Health Organization classification defines IVLCL as an extranodal diffuse large B-cell lymphoma. Its atypical presentation often delays the diagnosis and due to its aggressive behavior, unfortunately the diagnosis is made postmortem in half of the cases. However, if diagnosed early, IVLCL is potentially treatable. 
In our case, the report of the patient's bone marrow biopsy after death of the patient revealed the presence of IVLCL. After availability of final diagnosis, we reviewed the literature and a better explanation of the 18-flurodeoxyglocose positron emission tomography-computed tomography (FDG PET/CT) findings could be obtained. It was the rapidly fatal course of this malignancy that prompted us for searching reasons of the unusual FDG PET/CT findings. "Mortui Vivos Docent" is a latin quote which means "The Dead teach the Living." This classical quote is used to justify dissections of human cadavers in order to understand the cause of death. Similarly in our case, the post-mortem diagnosis made us understand the cause of FDG PET/CT appearance.
| > Case Report|| |
A 62-year-old Indian male presented to the physician at a tertiary care hospital with history of low-grade fever since last 1 month, weight loss of 9 kg in the last 3 months and he was delirious from 1 week. His blood examination revealed thrombocytopenia and raised serum creatinine. His blood culture was negative for any microbial growth and despite empirical treatment with multiple antibiotics, he continued to have low-grade fever. Noncontrast computed tomography of chest and abdomen was reported as normal except for bilateral bulky adrenal glands. His bone marrow biopsy was performed and the report was awaited.
He was referred to our department for FDG PET/CT as a case of fever of unknown origin (FUO). His FDG PET/CT scan showed global, severe hypometabolism in brain [[Figure 1], block arrow]. Being an obligate glucose consumer, brain is usually one of the most metabolically active (and hence FDG-avid) organs. Diffuse, low-grade FDG uptake was noted in bilateral lung fields (blue arrows). The maximum standardized uptake value (SUVmax) of FDG uptake in lungs was 0.8 cm 2 /mL. Transaxial CT and fusion PET/CT images show hypermetabolism in bilateral, bulky adrenal glands [[Figure 2], arrows] and increased metabolic activity in bone marrow [[Figure 3] arrows]. The SUVmax in right and left adrenal glands was 2.3 and 2.6 cm 2 /mL respectively. The SUVmax of bone marrow was 2.1 cm 2 /mL. None of the FDG PET lesions showed no obvious abnormalities on noncontrast CT. Contrast enhanced CT was not performed due to deranged renal function. No evidence of metabolically active lymphadenopathy or hypermetabolic spleen was noted. Considering the hypermetabolism in marrow and adrenal glands, the possibility of lymphoproliferative disorder was raised in the report. However, no definitive explanation of all the findings could be offered. Serum lactate dehydrogenase was ordered and was found to be 520 units/L (normal 150--450 units/L). Unfortunately before receiving any definitive treatment, the patient expired 3 days after FDG PET/CT was performed. In our case, the report of the patient's bone marrow biopsy, which became available after the patient's death, revealed the presence of IVLCL.
|Figure 1: Maximum intesity projection image of PET/CT showing generalized, severely reduced FDG uptake suggesting significant hypometabolism in brain (black arrow). Being an obligate glucose consumer, brain is usually one of the most FDG avid organs. There is low-grade diffuse FDG uptake in bilateral lungs (blue arrows). The intense FDG uptake marked with red arrow represents retained FDG in the patient's intravenous catheter|
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|Figure 2: Transaxial CT and FDG PET/CT images demonstrate increased FDG uptake in bilateral bulky adrenal glands (arrows). The SUVmax in right and left adrenal glands was 2.3 and 2.6 cm2/mL respectively. Hypermetabolism in bilateral adrenal glands is considered to be due to direct invasion of this highly vascular organ by neoplastic cells of IVLCL and such involvement may complicate into adrenal insufficiency|
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|Figure 3: Sagittal PET and Fused PET/CT images reveal diffuse hypermetabolism in marrow. The SUVmax of bone marrow was 2.1 cm2/mL. It was the biopsy of bone marrow that lead to final diagnosis of IVLCL|
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| > Discussion|| |
To correlate FDG PET/CT findings with the final histopathological diagnosis we did a review of the literature describing imaging characteristics of this rare malignancy. Nonspecific findings on blood examination and negative imaging studies complicate a prompt and accurate diagnosis. Laboratory findings that can be encountered include anemia (63 to 65%), an increased LDH (80 to 90%), and an elevated ESR (43%).Computed tomography (CT) is frequently not supportive because lymphadenopathy and hepato-splenomegaly are usually absent. 
Common symptoms derive from skin or brain involvement, of which at least one is observed in two-thirds of cases. The clinical presentation is too variable to guide toward the diagnosis. However in an effort to help clinicians Masaki et al. proposed "early clinical diagnostic strategy" for diagnosis of IVLCL. The criteria include early clinical diagnostic strategy for starting treatment for IVLCL patients with quite poor performance status (PS) and in whom time is a limiting factor: (1) age>40 years, (2) fever above 38° C with poor PS (ECOG 2--4), (3) lactate dehydrogenase (LDH) more than twice the upper limit of the normal level and/or soluble interleukin-2 receptor >5,000 IU/mL in serum, (4) worsening PS and/or elevation of serum LDH on a daily basis, and (5) confirmation of pathological lymphoid cells in peripheral blood or bone marrow smear and/or flow cytometry. Although accurate pathological diagnosis is quite important, time is a limiting factor for most of IVLCL patients. In such cases, chemotherapy can be started, based on early clinical diagnostic strategy with high sensitivity and good clinical outcome can be obtained. 
There are scarce data available on FDG PET/CT findings in IVLCL and is mainly in the form of case reports. ,,,,, Successful use of FDG-PET in diagnosing IVLBCL in cases of fever of unknown origin, which is common presentation of this disease, has been described in few case reports.
Brain being an obligate glucose user is usually one of the most FDG avid organ showing intense tracer uptake. Severe, global hypometabolism in the brain on FDG PET/CT have been reported as findings in IVLCL.  IVLCL is characterized by the presence of neoplastic lymphocytes only in the lumina of small vessels. The neoplastic cells cannot reach the parenchyma because of the loss of adhesion molecules during malignant transformation. Multifocal vascular occlusions caused by proliferation of malignant lymphocytes in the lumen result in diffuse thrombosis and tissue infarction. , Such micro-infarctions can lead to severe hypometabolism noted in brain. Apart from IVLCL as described in our case, the other causes of hypometabolism in brain are comatose patient, multifocal cerebral infarctions, treatment with sedatives or corticosteroids and the "Metabolic Super scan." In metabolic superscan there is reduced FDG uptake in brain because of most of the injected FDG is concentrated in the extracranial neoplasm.  Hence hypometabolism in brain as an isolated finding on PET/CT should be interpreted with caution.
Another reported characteristic feature on FDG PET/CT is hypermetabolic bilateral adrenal glands. Hypermetabolism in bilateral adrenal glands is considered to be due to direct invasion of this highly vascular organ by neoplastic cells and such involvement may complicate into adrenal insufficiency. Tumor mass may also compress the adrenal parenchymal cells, resulting in cell atrophy and organ dysfunction. Adrenal insufficiency may manifest subclinically or present with overt Addisonian symptoms although adrenal insufficiency as a cause of death is rare. Most of the patients reported to have adrenal involvement were older than 60 years, with female preponderance. ,
Increased FDG uptake in bone marrow and lung that was proven to be due to IVLCL on biopsy has been described in past. , Other findings reported in the literature in cases of IVLCL include diffuse FDG uptake in kidneys and lungs with no obvious CT demonstrable abnormality.  In cases of IVLCL involving lung, diffuse ground glassing in lungs may or may not be seen on CT. Thoracoscopic lung biopsy can be used for obtaining tissue diagnosis. On histopathology accumulation of malignant lymphocytes within alveolar capillaries, pulmonary veins, and peribronchial arterioles is noted. Damage to the construction of the alveoli, necrosis, and hemorrhage is also seen. In addition to this infiltration of tumor cells show spread into the capillaries, which is similar to vasculitis such as necrotizing vasculitis or Wegener's granulomatosis. However, in these diseases, the cells infiltrate to the vessels' walls and do not infiltrate into the lumens of vessels. In IVLCL the lymphoma cells infiltrate and occlude the lumen of the vessels. 
In IVLCL, lymphadenopathy or abnormalities in spleen are characteristically absent.  In suspected or known patients of lymphoma, the absence of lymphadenopathy on pretherapy PET/CT is a vital finding, pointing toward extranodal disease.  FDG PET/CT of our patient showed marked hypometabolism in brain, hypermetabolism in bilateral adrenal glands and bone marrow as well as low-grade diffuse FDG uptake in lungs. There was no lymphadenopathy. We found, retrospectively, that our patient had the scan features that fit into typical findings of IVLCL.
Patients with IVLCL need to be treated with systemic chemotherapy as any disseminated malignant disease. Anthracycline-based chemotherapy is considered first-choice therapy, as results of other chemotherapeutic regimes have been disappointing.  In the case of CNS involvement, CNS-oriented chemotherapeutic agents, such as methotrexate or cytarabine, should be added. However, despite intensive chemotherapy, recurrence of disease is seen in more than half of the cases with an ultimately poor prognosis.  A recent retrospective study showed promising results from the addition of rituximab, the standard therapy for CD20-positive lymphomas, improving disease-free and overall survival. , Nevertheless, the optimal treatment of this rare distinct variant of non-Hodgkin's lymphoma, with a largely unknown biological behavior, remains unclear.
In conclusion, our case had characteristics features of IVLCL on FDG PET/CT which could be linked together to a common pathology (IVLCL), only after having a postmortem tissue correlation. We describe this case, to call for heightened awareness in physicians for the rare but possible diagnosis of IVLCL, particularly in an elderly patient who presents with FUO and demonstrates similar FDG PET/CT findings. This case report demonstrates the potential value of FDG-PET/CT in unexplained neurological illness and fever, with a small but evident chance of finding a clue to the unique diagnosis of IVLCL. Considering the characteristic scan findings described in our patient and other cases in the literature, FDG PET/CT can be used in suspected cases of IVLCL for early diagnosis of this rapidly fatal malignancy.
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[Figure 1], [Figure 2], [Figure 3]