CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis:A clinical-pathological study

Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

Pilomyxoid Astrocytoma in Cerebellum

Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum.MRI scanning showed a tumor involved the cerebellar vermis,tonsil,the forth ventricle and brainstem.It was homogeneous isointensity on T1WI,relative hyper-intensity on T2WI,hyper-intensity on fluid attenuated inversion recovery （FLAIR） images,and uniform enhancement on contrast T1WI.The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma.Follow-up at the 5th month,MRI showed the residual tumor enlarged at the brainstem.The patient survived 10 months after the operation,and finally died of respiration failure resulting from brainstem dysfunction.

IgG4-related autoimmune pancreatitis overlapping with Mikulicz's disease and lymphadenitis:A case report

Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-IgG4-related disease.We report a case of IgG4-related AIP overlapping with Mikulicz’s disease and lymphadenitis,which is rare and seldom reported in literature.A 63-year male from Northeast China was admitted for abdominal distension lasting for one year.He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo.He had a 2-year history of bilateral submandibular lymphadenopathy without pain.He underwent surgical excision of the right submandibular lymph node one year prior to admission.He denied any history of alcohol,tobacco,or illicit drug use.Serological examination revealed high fasting blood sugar level(8.8 mmol/L)and high level of IgG4(15.2 g/L).Anti-SSA or anti-SSB were negative.Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation.Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens.The patient received a dose of 30 mg/d of prednisone for three weeks.At this three-week follow-up,the patient reported no discomfort and his swollen salivary glands,neck lymph node and pancreas had returned to normal size.The patient received a maintenance dose of 10mg/d of prednisone for 6 mo,after which his illness had not recurred.

Subcutaneous panniculitis-like T-cell lymphoma invading central nervous system in long-term clinical remission with lenalidomide:A case report

BACKGROUND Subcutaneous panniculitis-like T-cell lymphoma(SPTCL)involvement in the central nervous system(CNS)is particularly rare.SPTCL with CNS involvement has an exceedingly poor prognosis,and no optimum therapeutic method has been discovered.To the best of our knowledge,this is the first reported case of SPTCL invading the CNS achieving long-term remission with lenalidomide maintenance therapy.CASE SUMMARY A 63-year-old man diagnosed with SPTCL was admitted to the hospital with severe headache for 15 d after four cycles of chemotherapy.Subsequent to the treatment,the patient developed CNS involvement.Craniotomy biopsy was pathologically diagnosed as CNS T-cell lymphoma,and two courses of chemotherapy were performed postoperatively.Due to the intolerance of the side effects of chemotherapeutic drugs,the patient received lenalidomide instead.The magnetic resonance imaging of the head at the 8 mo follow-up indicated no signs of recurrence,and the vital signs were stable.CONCLUSION Lenalidomide deserves further investigation as a targeted drug for SPTCL cases involving the CNS.

Paraplegia from spinal intramedullary tuberculosis:A case report

BACKGROUND Tuberculosis (TB) mostly attacks the lungs, and extrapulmonary TB involving thecentral nervous system is uncommon;among these cases, spinal intramedullaryTB is even more rare. The clinical manifestations of spinal intramedullary TB aresimilar to those of intramedullary spinal cord tumors. Therefore, it is necessary tomake a careful differential diagnosis of spinal intramedullary lesions to achievethe appropriate treatment and favorable prognosis. We report a rare case of ayoung male patient with paraplegia due to spinal intramedullary TB, which isuncommon and regrettable.CASE SUMMARY A 23-year-old male presented with fever accompanied by nausea and vomitinglasting for 2 mo and was then diagnosed with tubercular meningitis. After anti-TBtreatment, his symptoms were significantly improved. However, 2 mo after thediagnosis of tubercular meningitis, the patient felt numbness below the costal archlevel, which lasted for 1 wk, and he paid no attention to this symptom. Whatfollowed was paraplegia and urine/fecal incontinence. Magnetic resonanceimaging of the thoracic spine showed a ring-enhanced intramedullary cord lesionat T8-T9. Lesion exploration showed enlargement of the spinal cord at T8-T9, andthe lesion could be observed by incision. The lesion was adhered to the peripheraltissue and was grayish-white and tough with a poor blood supply and a diameterof approximately 0.8 cm. The lesion was resected completely. The results ofpathological examination by both hematoxylin-eosin staining and acid-fast bacillistaining confirmed TB, accompanied by acute and chronic suppurativeinflammation and granulation tissue formation. The patient was instructed tocontinue anti-TB treatment after the operation, but he did not follow the medicaladvice. Follow-up continued for ten years, the patient had persistent paraplegia,the numbness disappeared and urine/fecal sensation recovered.CONCLUSION Although TB is a kind of benign disease, some cases progress rapidly. Moreover,spinal intramedullary TB may seriously endanger quality of life and still needstimely diagnosis and proper treatment.