Kimura's disease and ankylosing spondylitis: A case report.

RATIONALE: Ankylosing spondylitis (AS) and Kimura's disease (KD) which is quite rare are both chronic inflammatory diseases. Recently we encountered a patient who suffered from KD and AS, and some of his family members also suffer from AS. We, therefore, investigated this unique case and conducted the family-based whole exome sequencing to explore the possible genetic alterations. PATIENT CONCERNS: Here, we reported a case of a 44-year-old Chinese man with multiple painless masses all over his body and a back pain for 32 years. His uncle and sister were diagnosed with AS. DIAGNOSIS: The diagnosis of KD was based on the patient's clinical features and the biopsy of the neck masses. The diagnosis of AS was based on the patient's clinical features, HLA-B27(+) and the radiologic changes of sacroiliac joints. The genetic test showed that ARPC1B gene which was associated with recurrent infections, auto-inflammatory changes and elevated IgE levels was mutated in this patient. INTERVENTIONS: Neck masses were removed by surgery. Systemic glucocorticoid, nonsteroidal anti-inflammatory agents, combined with cyclosporine were orally administered, and Etanercept was injected subcutaneously. OUTCOMES: The masses disappeared rapidly after surgery combined with systemic glucocorticoid, but relapsed shortly after the therapy was discontinued. Low dose glucocorticoid, cyclosporine and Etanercept could keep both KD and AS remained long-term remission. LESSONS: Our experience suggests that low dose glucocorticoid, cyclosporine and Etanercept could be beneficial for the patient with KD and AS. The mutation of ARPC1B gene in this case, which is associated with immunologic disturbance, may increase the susceptibility of KD.

Cutaneous intravascular epithelioid hemangioma. A clinicopathological and molecular study of 21 cases.

Pure intravascular growth of epithelioid hemangioma (EH) is exceptional. Herein, we report a series of 21 intravascular EHs, representing a potential serious diagnostic pitfall by mimicking malignant vascular neoplsms with epithelioid morphology. The tumors developed in 12 males and 4 females, aged from 11 to 71 years (mean age 40.2 years) with a predilection for the extremities (13 of 21, 61.9%), followed by the head and neck (8 of 21, 38.1%). Lesions ranged in size from 2 to 30 mm (mean size 13 mm). The most common presenting feature was a slowly growing nodule. Most neoplasms were solitary (13 of 16 patients, 81.2%) but three patients developed more than one intravascular EH (3 of 16, 18.8%). Treatment consisted of complete surgical excision and was generally curative. Follow-up was available for 13 lesions that had developed in ten patients (range 4-72 months, mean 27.3 months). No recurrences or development of additional tumors were observed. All 21 lesions developed in subcutaneous veins. Two morphological patterns of intravascular epithelioid endothelial cell proliferation were observed: (1) a lobular capillary hemangioma-like proliferation with variable formation of open vascular lumina and (2) a solid proliferation generally lacking open vascular spaces. A lobular capillary hemangioma-like pattern was the sole pattern in nine lesions, a mixed lobular hemangioma-like pattern, and solid pattern in eight and a pure solid pattern in four intravascular EHs. Mitotic activity in epithelioid endothelial cells ranged from 0 to 7 mitoses per 10 high-power field (mean 2.1 mitoses per 10 HPFs). Six lesions displayed brisk mitotic activity of five or more mitoses per 10 HPF (6 of 21, 28.5%). The number of mitoses was usually more prominent in areas with solid growth. Atypical mitoses were not observed. No intratumoral necroses were seen. Cytological atypia was mild (20 out of 21 cases). By immunohistochemistry, all tumors were positive for CD31 (14 out of 14) and ERG (5 out of 5). While all tested cases were FOS negative by immunohistochemistry (6 out of 6), one out of six cases (case 6) displayed FOSB nuclear positivity in about 30% of the lesional endothelial cells. Eight cases were analysed by FISH for the presence of FOS and FOSB gene rearrangements. While all cases were negative for FOSB rearrangements, a single case proved positive for FOS gene break-apart. In conclusion, intravascular growth of EH is not associated with adverse biological behavior. Solid intravascular proliferations of endothelial cells can mimic a malignant vascular tumor with epithelioid morphology. Nevertheless, intravascular EHs display mild cytological atypia coupled with low mitotic activity, and a lack of atypical mitoses, pronounced nuclear atypia, multilayering or tumor necrosis. Finally, the FOS gene is infrequently rearranged, and there are no FOSB gene abnormalities in this subset of EHs, suggesting a potential distinct pathogenesis than most classic EHs.

Kimura's disease and Behcet's syndrome in the same family--are they associated?

BACKGROUND: Behcet's disease (BD) and Kimura's disease (KD) are two inflammatory diseases commonly found in Japan. In Israel, both diseases are quite rare. Recently, we encountered a family whose three siblings suffer from BD and an additional brother suffers from KD. This observation raised the question as to whether both diseases have a common underlying genetic basis. AIM OF THE STUDY: To describe this unique family and to search for possible common alleles in the IL10 gene between BD and KD, as several SNPs in this gene are known to be associated with BD. METHODS: Three BD siblings and their brother with KD were interviewed and examined. Genomic DNA was prepared from blood samples taken from all nine members of the family. The DNA was genotyped for sequence variations of six SNPs on the IL10 gene. RESULTS: The IL10 SNPs did not segregate with BD and KD suggesting that there was no association between the IL10 gene and these diseases in this family. CONCLUSIONS: SNPs in the IL10 gene shown to be susceptibility factors in adult BD were not associated with BD in this family. The question regarding a possible common genetic basis for KD and BD requires further investigation.

Analysis of Clonality in Kimura's Disease.

Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 62-year-old man presented with asymptomatic cervical lymphadenopathy associated with eosinophilia and increased serum immunoglobulin E. Excision biopsy showed Kimura's disease. Three years later another groin lymph node appeared and showed similar pathologic features. Polymerase chain reaction for Ig heavy chain and T-cell receptor (TCR) genes on DNA extracted from the cervical lymph node showed smear patterns. However, polymerase chain reaction for TCRdelta gene showed a clonal rearrangement. Sequencing showed a complete VDJ rearrangement (Vdelta1-N-Ddelta2-N-Jdelta), confirming the presence of a clonal T cell population. The same clonal TCRdelta rearrangement was amplified by polymerase chain reaction from the groin lymph node biopsied 3 years later. These results showed that the primary and recurrent lesions were biologically related. Furthermore, the presence of identical T cell clones in different sites and at different times suggested that a clonal T cell population might have contributed to the pathogenesis in this case of Kimura's disease.

IL-5 mRNA expression in blood lymphocytes from patients with Kimura's disease and parasite infection.

Blood lymphocytes from patients with eosinophilia are known to produce interleukin-5 (IL-5) with appropriate stimulation in vitro. To determine whether blood lymphocytes from these patients produce IL-5 in vivo, we tested the IL-5 mRNA expression in blood lymphocytes immediately after separation by reverse-transcriptase polymerase chain reaction (RT-PCR) method. We found that lymphocytes from eosinophilic patients expressed IL-5 mRNA, but lymphocytes from normal volunteers did not express the lymphokine. These findings suggest that in patients with eosinophilia, peripheral blood lymphocytes produce IL-5 in vivo.