Case 1 is a 16-year-old boy. He was admitted to hospital because of "abdominal mass accompanied by fever, oral ulcer and shortness of breath for one and a half years and worsened for three months". In January 2008, the patient found an abdominal mass without obvious inducement, accompanied by oral ulcer, fever, shortness of breath, cough, expectoration, abdominal pain, abdominal distension, no fatigue, night sweats, poor tolerance, no discomfort such as dry mouth, dry eyes, joint pain, and no special treatment was conducted. In late March 2009, the patient developed shortness of breath, obvious during activities, and no chest tightness or chest pain. Then admitted to hospital on 2 June 2009. Physical examination on admission: splenomegaly, a mass could be palpated in the abdomen, lymph nodes of the size of soybeans could be palpated in both groins, and rales of dry and wet could be heard in both lungs. Blood routine: WBC: 10.31×10E9/L, HB119g /L, PLT: 286×10E9/L, N%: 0.67, L%: 0.251; Albumin: 27.5g/ L, Globulin: 26.5g/ L, A/G:1.02; CRP: 1.8mg/ L; IgM: 2.52g/ L, IgG: 11.69g/ L, IgA: 1.73g/ L; Autoantibodies: histone (+/-), keratin antibody (+), anti-nuclear antibody (+), anti-DS-DNA (+/-), anti-cardiolipin antibody (+); T lymphocyte subsets: total T cells: 78.2%, CD4+ cells: 39.4%, CD8+ cells: 33.4%, CD4/CD8 ratio: 1.18; Blood gas analysis: pH :7.434, PO2:78.4mmHg, PCO2:42.7mmHg, HCO3:28; Plain CT scan of chest and abdomen: 1. Huge space occupying lesion in the right posterior abdominal cavity. 2. splenomegaly. 3. Emphysema, infectious lesions in the anterior segment of the right upper lobe.4. Endogenous gas in the mediastinum and posterior chest wall. (Figure 1). Pulmonary function examination: FEV1%: 23.3%, FVC%: 67.2%, FEV1/FVC: 28.96%, suggesting: 1. Severe obstructive ventilation dysfunction. 2. Peripheral resistance, total airway resistance Peripheral elastic resistance increased. Bronchial dilation test: absolute value of FEV1 increased by 70ml. Right posterior abdominal mass resection was performed during hospitalization. Postoperative pathology showed Castleman's disease of lymph node HV. Oral mucosal biopsy showed slight epithelial hyperplasia, basal cell liquefaction, no spinous layer release, vascular hyperplasia in lamina propria, lymphocyte infiltration. Accompanied by ulcer formation, ulcer surface has vascular hyperplasia, lymphocytic infiltrate. Diagnosis: 1. Multicentric transparent vascular Castleman's disease (left neck, right supraclavicular, bilateral axilla, inguinal lymph nodes); 2. Paraneoplastic pemphigus; 3. Bronchiolitis obliterans. No significant improvement was observed after the treatment of methylstrongone, aminophylline and bronchodilator. The symptoms were not improved after the treatment of COP regimen combined with interferon and CHOP regimen. He was subsequently loss to follow-up.
Case 2: A 51-year-old man was admitted with "cervical lymph node enlargement with exertive shortness of breath for 1 month". On October 10, 2011, he went to a local hospital due to "inguinal hernia". After physical examination, cervical lymph node enlargement was found. PET/CT examination showed multiple nodules under the left neck, bilateral clavicle region and mediastinum, with uneven increase in metabolism. Pathological examination of the left cervical lymph node showed HV of giant lymph node hyperplasia (Castleman's disease). The patient was gradually accompanied by weight loss, shortness of breath, blood sputum, right chest pain and oral ulcer. No fever, night sweats, abdominal pain, diarrhea, rash or joint pain were found. No special treatment was given, and the mass in the left neck was larger than before. He went to our hospital for further diagnosis and treatment on November 8, 2011. On admission, physical examination showed that there were several lymph nodes of soybean size in the left neck and supraclavicular fossa. Dry and wet rales can be heard in both lungs. Blood routine examination at admission: WBC: 7.6×10E9/L, N%: 0.548, L%: 0.208, Hb:146g/ L; Albumin: 44.5g/ L, Globulin: 27.5g/ L, A/G:1.8; IgM: 1.693g/ L; PLT: 286×10E9/L. Renal function: Creatinine 100μmol/L, endogenous creatinine clearance rate 57ml/min; T cell subsets: CD4+T cells: 28.10%, CD8+T cells: 41.20%, CD4/CD8:0.68, total T cells: 75.50%. IgG, IgA, liver function and urine routine examination showed no abnormality. Blood gas analysis: pH :7.352, PO2:120mmHg, PCO2:46.5mmHg, HCO3- : 24.1 (oxygen absorption, 2L/min). Chest CT: Multiple mediastinal lymphadenopathies (Figure 2). Diagnosis: Multicenter clear vascular Castleman's disease (left lower neck, bilateral clavicular region, mediastinal lymph node). After four cycles of chemotherapy in CHOP regimen, and no significant reduction of mediastinal lymph nodes was observed. The fifth and sixth cycles of chemotherapy were changed to FCD regimen. On December 8, 2011, chest CT was conducted and result revealed: Mediastinal multiple lymph node enlargement was slightly smaller than before. In January 2013, he began to develop oral ulcer, which was diagnosed as "pemphigus" by the affiliated stemmatological hospital. He was treated with 2 capsules of compound hydrocortisone three times a day, but there was no obvious improvement of oral ulcer. He stopped taking hormones in November 2013 and gradually developed discomfort such as shortness of breath after activity. So, he returned to the hospital for treatment due to cough, sputum and shortness of breath after activity, during hospitalization, lung function examination was performed and result as follows: FEV1%:18.8%, FVC%:48.6%, FEV1/FVC:31.5%, VC%:46.9%, volume of dispersion: 0.49%, rate of dispersion: 0.33, RV/TLC: 78.01. Conclusion: 1. Severe obstructive ventilate dysfunction; 2. Severe peripheral airway obstruction; 3. Severe diffuse dysfunction; bronchial dilation test: 20 minutes after inhalation of Ventolin, FEV1 increased by 16.9%, and the absolute value of FEV1 only increased by 90ml. Chest CT: Patchy, cable-like high-density and ground-glass shadows were seen in both lungs, and multiple enlarged lymph node shadows were seen in the mediastinum. Diagnosis: 1. Castleman's disease 2. Paraneoplastic pemphigus 3. Interstitial pneumonia. The patient was given piperacillin sodium tazobactam, levofloxacin and fluconazole for anti-infection. After discharge, the patient was voluntarily switched to itraconazole but still with mild symptoms. Later, he was admitted to hospital because of "cough, sputum, shortness of breath" and other symptoms, no significant improvement was found but gradually worsened. The reexamination of chest CT indicated that mediastinal lymph nodes disappeared, but the lung lesion is irreversible with cavitation and always visited hospital for respiratory infection.
Case 3: A 63-year-old female was admitted with "left chest and left lower abdominal pain for more than 1 month". She felt paroxysmal dull pain in left chest and left lower abdomen with no obvious cause early in January 2012, with oral ulcer, fearless cold, fever, nausea, vomiting, diarrhea, no chest tightness, shortness of breath and other discomfort, pain gradually aggravated, and affected sleep. Thus, she went to the local hospital, abdominal ultrasound was conducted but no obvious abnormity was seen. Chest CT found: Patchy high-density shadow can be seen in both lungs, soft tissue mass shadow can be seen protruding into the left thoracic cavity near the spine of the left lower lung, irregular thickening and envelopment of the left pleura, lymph node shadow of mediastinal tracheal bulge. After that, a series of symptoms, namely cough with a little white foam-like sputum, appetite decreased, fatigue occurred. For further diagnosis and treatment, she was admitted to our hospital. Physical examination on admission: right supraclavicular lymph node enlargement. Complete blood routine examination: WBC 9.1×10E9/L, Hemoglobin 103g/ L, PLT 523×10E9/L; Albumin: 29.2g/ L, Globulin: 41.5g/ L, A/G:0.7; CRP: 31.13mg/L; IgM: 1.16g/ L, IgG: 20.27g/ L, IgA: 4.03g/ L; Autoantibodies: Anti-RO-52 antibody (+), and the remaining index were negative. No abnormalities of renal function, routine urine and complement were observed. Pulmonary function examination: FEV1%:69.4%, FVC%:77.6%, FEV1/FVC:73.32%, VC%:77.1%, volume of dispersion: 1.62%, dispersion rate: 1.46%, RV/TLC: 46.18. Conclusion:1. Mixed ventilatory dysfunction with mild limitation. 2. Mild peripheral airway obstruction. Chest CT: Patchy high-density shadow in both lungs, irregular thickening of the left pleura with envelopment, and lymph node shadow in mediastinal trachea. Fiber bronchoscopy showed chronic bronchitis, a small amount of lung tissue, clear alveoli, no tumor. B-mode ultrasound: Multiple enlarged lymph nodes in the left neck and right supraclavicular, multiple hypoechoic masses in bilateral axilla and inguinal region (lymph node sonography). Percutaneous lung penetration of the lower left lung mass: Microscopic observation showed fibrous connective tissue, hyalinosis and small focal-like chronic inflammatory cell infiltration, no histological evidence of granuloma or carcinoma. The microscopic examination of lymph nodes in the left neck showed structural destruction of lymph nodes, atrophy of lymphatic follicles, hyperplasia of interstitial fibrous tissue with hyalinosis, and hyalinosis in the vascular wall, which was consistent with giant lymph node hyperplasia (clear vascular type). Diagnosis: 1. Multicentric Castleman's disease of HV (left neck, right supraclavicular, bilateral axilla, inguinal lymph nodes); 2. Paraneoplastic pemphigus; 3, bronchitis obliterans. After receiving anti-inflammatory, analgesic and other symptomatic supportive treatment, it was suggested to consult the thoracic surgery department to evaluate whether surgical treatment could be performed, but the patient refused and asked to be discharged when the condition did not improve and soon died of respiratory failure.
Summary of the 3 case
Two of the three patients with the mediastinum involved, and their clinical manifestations included cough, expectoration, shortness of breath, chest pain and other common symptoms of respiratory diseases. Meanwhile, all the three patients had refractory oral ulcer, systemic symptoms such as emaciation, fever, splenomegaly, and local compression symptoms such as local lymph node enlargement or abdominal pain. With respect to laboratory examination, anemia is more common. At the same time erythrocyte sedimentation rate, CRP, immune globulin elevated, albumin declined. Chest CT mainly showed bronchiectasis and mediastinal lymph node enlargement, with flocculent, patchy and stripe high-density shadow. Blood gas analysis showed hypoxemia and pulmonary function examination showed obstructive ventilation dysfunction, among which 1 case was mixed ventilation dysfunction with mild restrictive ventilation dysfunction. The bronchial dilation test was normal. Physical examination and other auxiliary examinations confirmed the polycentric diagnosis of CD.
Table 1 General information and clinical manifestations of the 3 cases of HV-MCD
Case
|
Age(Year)
|
Gender
|
Occupation
|
Clinical features
|
Involved regions
|
P1
|
16
|
Male
|
Student
|
Fever, weight loss, shortness of breath, cough, sputum, abdominal pain, abdominal distention, oral ulcer, splenomegaly
|
Oral mucosa, abdominal cavity, bilateral inguinal lymph nodes
|
P2
|
51
|
Male
|
Teacher
|
Neck lymph node enlargement, weight loss, shortness of breath, bloody sputum, chest pain, oral ulcer
|
Bilateral neck, supraclavicular fossa, mediastinum, abdomen
|
P3
|
63
|
Female
|
Worker
|
Chest pain, abdominal pain, oral ulcer
|
Left neck, left supraclavicular fossa, mediastinum
|
Table 2. Laboratory test results of the 3 cases of HV-MCD
|
P1
|
P2
|
P3
|
WBC(3.5-9.5)(×109/L)
|
10.31
|
7.6
|
9.1
|
HGB(130-150)(g/L)
|
119
|
146
|
103
|
PLT(125-350)(×109/L)
|
329
|
286
|
523
|
N%(0.4-0.75)
|
0.67
|
0.548
|
0.696
|
L%(0.2-0.5)
|
0.251
|
0.208
|
0.145
|
ESR(0-15) (mm/h)
|
-
|
-
|
84
|
CRP(0-5)(mg/L)
|
1.8
|
-
|
31.13
|
ALB(40-55)(g/L)
|
27.5
|
44.5
|
29.2
|
GLB(20-40)(g/L)
|
26.5
|
27.5
|
41.5
|
A/G(1.2-2.4)
|
1.02
|
1.8
|
0.7
|
C3(0.79-1.52)(g/L)
|
1.15
|
-
|
1.35
|
C4(0.16-0.38)(g/L)
|
0.34
|
-
|
0.37
|
IgM(0.840-1.32)(g/l)
|
2.52
|
1.693
|
1.16
|
IgG(8-18)(g/l)
|
11.69
|
normal
|
20.27
|
IgA(0.9-4.5)(g/l)
|
1.73
|
normal
|
4.03
|
Creatinine(59-104)(umol/L)
|
normal
|
normal
|
normal
|
RF(0-12.5)(IU/ML)
|
2.6
|
-
|
5.3
|
Autoantibody
|
Histone(+/-), AKA(+) ANA(+), anti-ds-DNA(+/-), ACA(+)
|
-
|
Ro-52(+)
|
Tumor marker
|
Normal
|
-
|
normal
|
T cell subsets
|
Total T: 78.2%, CD4+T:39.4%, CD8+T:33.4%, CD4/CD8: 1.18
|
TotalT:75.50%, CD4+T:28.10%, CD8+T:41.20%, CD4/CD8:0.68
|
-
|
Table 3 Instrumental examination results of the 3 cases of HV-MCD
|
P1
|
P2
|
P3
|
ECG
|
Sinus arrhythmia
|
Sinus rhythm, T wave changes
|
Normal ECG
|
Abdominal ultrasound
|
Right abdominal mass of substance
|
Liver inner gallbladder wall thickened, echo enhancement, gallbladder stone.
|
Normal
|
Urinary ultrasound
|
-
|
The left kidney cyst
|
Normal
|
Others
|
Abdominal CT plain and enhanced: 1. Huge space occupying lesion in the right posterior abdominal cavity. 2. splenomegaly
|
PET/CT: Multiple nodules under the left neck, bilateral clavicle area, and mediastinum, with uneven metabolism and increased, with high possibility of lymph nodes, gallbladder stones, and small left renal cyst considered.
|
B ultrasound: Uterorectal depression and liquid dark area, 20×13cm.Suggest pelvic effusion.
|
Table 4 Results of blood gas analysis, respiratory function and bronchodilation test in 3 cases of HV-MCD
|
P1
|
P2
|
P3
|
FEV1%
|
23.3
|
18.8
|
69.4
|
FVC%
|
67.2
|
48.6
|
77.6
|
FEV1/FVC
|
28.96
|
31.5
|
73.32
|
VC%
|
67.1
|
46.9
|
77.1
|
Bronchial dilation test
|
The absolute value of FEV1 was increased by 70ml
|
The absolute value of FEV1 was increased by 90ml
|
Negatice
|
Diffusing capacity
|
-
|
0.49
|
1.62
|
Dispersion rate
|
-
|
0.33
|
1.46
|
RV/TLC
|
-
|
78.01
|
46.18
|
PH
|
7.434
|
7.352
|
-
|
PO2(mmHg)
|
78.4
|
120*
|
-
|
PCO2(mmHg)
|
42.7
|
46.5
|
-
|
HCO3-
|
28
|
24.1
|
-
|
* The concentration of oxygen inhalation was 3L/min