Inexplicable intracranial lesions, the director shared the diagnosis process, it was wonderful!

*Only for medical professionals to read the reference and leave a question at the end of the article, welcome to share your views in the message area! At the 24th National Neurology Academic Conference of the Chinese Medical Association, Professor Lu Aijun from the 960th Hospital of the People's Liberation Army brought us a special case of "intracranial lesions", let's take a look Wonderful diagnostic process! Case Review Male, 22 years old, farmer
.

Chief complaint: intermittent fever, vomiting for more than 8 months, episodic loss of consciousness, limb convulsions for 3 months
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Date of admission: December 25, 2020
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[End of 2020.
04] The patient developed intermittent fever with a maximum of 38.
3 degrees, irregular, accompanied by vomiting, and occasionally sprayed, about 1 time per day, and continued to have repeated fever after treatment (specific details are unknown)
.

[2020.
06.
18] Local head CT (Fig.
1) showed bilateral frontal and parietal lobes with symmetrical large hypodensity; blood routine and liver function were generally normal, and no relevant treatment was performed
.

Figure 1 Brain CT on June 18 showed bilateral frontal and parietal lobes with symmetrical large hypodensity [2020.
06.
24] Brain MRI showed bilateral frontal lobes, basal ganglia, corpus callosum long T1 long T2, Flair, DWI, ADC high signal; Punctate and patchy enhancement in the lesion area
.

On June 30, the patient underwent MRI again.
Compared with June 24, the lesion area was reduced, and the signal in the DWI phase gradually increased
.

Figure 2 Cranial MRI on June 24th [2020.
7.
04] 1.
The patient still had repeated fever and no vomiting, so he went to the local hospital.
The internal medicine and nervous system examinations were normal
.

2.
Auxiliary examination: blood routine: lymphocyte ratio 16.
8%
.

TORCH: Herpes simplex virus type I+II lgM 2.
53↑, IgG>30↑ (0.
9-1.
1 Index)
.

Cytomegalovirus IgG 71↑ (12-14U/ml)
.

Tumor marker: NSE26.
7↑ (0-20 ng/ml)
.

Lumbar puncture: WBC 20x106/L↑; protein 0.
48↑; lgM1.
34↑ (<1.
30mg/L), lgA, lgG normal; cerebrospinal fluid BK virus, JC virus, EB virus, cytomegalovirus, herpes simplex type I virus, No pathogenic microorganisms were detected in Mycobacterium tuberculosis and Mycoplasma pneumoniae, and metagenomic detection was negative for DNA+RNA; lactate quantification was 2.
6↑ (1.
2-2.
1mmol/L); cytology: small lymphocytes 92%, general monocytes 8%
.

Echocardiography revealed mild mitral, tricuspid, and pulmonary regurgitation
.

The electroencephalogram was mildly abnormal (the voltage in the right posterior head area was low, with low amplitudes)
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Blood and cerebrospinal fluid oligoclonal (-), demyelinating antibodies (MOG, GFAP, AQP4), paraneoplastic antibodies (-); serum ANCN, antinuclear antibody spectrum, rheumatoid series, normal thyroid function; serum protein electrophoresis, infectious diseases Indicators are normal
.

Lung CT was normal
.

3.
Treatment: The patient improved after 10 days of antiviral and glutathione treatment [2020.
09.
01] The patient reappeared with episodic loss of consciousness, limb convulsions, trismus, and upturned eyes; gibberish, personality changes, and abnormal behavior
.

How to get to the bottom of it? 【2020.
12.
25】Transfer to the 960th Hospital of the People's Liberation Army for continued treatment
.

Past history, personal history, and family history were unremarkable
.

▌ Physical examination on admission: Physical examination of the internal medicine system was normal
.

Nervous system physical examination: euphoria, decreased advanced intelligence, obvious decrease in computing power, MMSE 15 points, normal cranial nerves, normal muscle strength and muscle tone of limbs, tendon reflexes (++), negative pathological signs, no deep and superficial sensations Abnormal, bilateral finger-nose test and heel-knee-shin test were stable and accurate, and the sign of difficulty with eyes closed was negative
.

The neck was soft and meningeal irritation was negative
.

▌ Auxiliary examination: blood routine, liver function, biochemistry, coagulation, and two stools were normal
.

Lumbar puncture: brain pressure 80mmH2O; white blood cells 6 x 106/L; protein 0.
56g/L↑, albumin 365mg/L↑, lgA 5.
62mg/L↑; exfoliated cytology showed a small amount of lymphocytes; cerebrospinal fluid bacteria, acid-fast bacilli, ink Stain (-), fungi and spores (-)
.

Blood Brucella (-), Epstein-Barr virus (-)
.

EEG: moderately abnormal EEG (20-50uV 2-4Hz complex slow wave with obvious limitations in bilateral frontal area, right central area and temporal area)
.

Considering that the herpes simplex virus of the patient was (+) in the local hospital, the patient was repeatedly checked 4 times, and the results showed: 1) 2021-01-01 I+II herpes simplex virus lgM 3.
2↑ (0.
9-1.
1Index) I+II type I+II simplex virus lgM Herpes virus IgG 30↑ (0.
9-1.
1Index) Cytomegalovirus IgG110↑ (0-12U/ml) 2) 2021-02-25I+II herpes simplex virus lgM 2.
7↑I+II herpes simplex virus IgG 30↑Giant Cytovirus lgG99.
6↑3) 2021-03-09 I+II herpes simplex virus lgM 1.
88↑4) 2021-03-18I+II herpes simplex virus lgM 2.
0↑ Then repeated two head MRIs, you can see To the lesion area gradually reduced, accompanied by atrophy of the cerebral cortex; enhancement was punctate or linear enhancement (Figure 3)
.

Figure 3 Comparison of 2020.
12.
29 and 2021.
01.
20 head MRI ▌ Treatment of acyclovir antiviral therapy, antiepileptic and hormone therapy
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▌ Localization, Qualitative Diagnosis Localization: cerebral cortex, frontotemporal lobe, based on: the patient's manifestations are euphoria, decreased advanced intelligence, epileptic seizures, and nonsense
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Qualitative: bilateral infiltrating white matter lesions, consider: 1) Infectious viral encephalitis? 2) Inflammatory tumor-like demyelination? Vasculitis? 3) Neoplastic gliomas? Lymphoma? ▌ To further confirm the diagnosis of brain tissue pathological biopsy: the formation of vascular lymphatic mantle (HE staining) in the submitted tissue, neuronal degeneration, gliosis, and scattered lymphocyte infiltration in the interstitium
.

Immunohistochemistry: CD3(+), CD43(+), CD20(+), CD79a(+), CD68(+), CD5(+), CD21(-), Bcl-2(+), MUM1(-) , P53 (scatter+), brain tissue GAFP and NF (+), Olig2 (+), MBP (+), S100 (+), CMV (-)
.

Ki-67 (about 2%)
.

In situ hybridization EBER(-)
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Gene rearrangement: lgH TubeC FR3-JH monoclonal hyperplasia
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▌ Pathological diagnosis of atypical hyperplasia of B lymphocytes
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Thinking 1.
For this patient, we most clinically suspect primary central nervous system lymphoma (PCNSL)? However, the patients were MUM1 negative, P53 scattered positive, and Ki-67 was about 2%.
The proportion was too low for the diagnosis of PCNSL.
Professor Lu pointed out, would this be a sentinel lesion (that is, the lymphoma is still on the way? It has not yet formed).
typical lymphoma-like lesions), or lymphoma-like granulomas? 2.
For lymphoma-like granulomas, it is usually EB virus-driven B lymphocyte proliferation.
However, in this patient, EBER was negative.
Instead, serum I+II herpes simplex virus IgG and IgG were positive many times, and lesions appeared in the later stage.
Partial brain atrophy
.

3.
Therefore, it is possible that the patient has persistent encephalitis caused by herpes simplex virus infection, and activates B lymphocytes through an immune-mediated mechanism, causing monoclonal proliferation, infiltration and destruction of blood vessels, and the formation of nest-like structures
.

4.
Brain atrophy may be associated with repeated infiltration and regression of extensive inflammatory cells in sentinel lesions? 5.
If the pathological changes of the patient are not tumor-like changes, could it be due to the simulated lymphoma-like lesions after virus infection? Regarding the thinking about the disease, teachers are also invited to express their opinions and discuss with each other, so that we can make progress together! The content of this manuscript is compiled in the wonderful lecture given by Professor Lu Aijun at the 24th National Neurology Academic Conference of the Chinese Medical Association
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