增生性肾小球肾炎伴单克隆IgG沉积及肾小球细胞内异常内含物

老年男性,慢性起病,临床表现为肾病综合征,少量镜下血尿,肾功能正常,高血压,轻度贫血,免疫固定电泳见κ型IgG单克隆免疫球蛋白条带。国家肾脏疾病临床医学研究中心首次肾活检示肾小球膜增生样病变,免疫荧光肾小球IgG3、κ轻链沉积为主,电镜下肾小球系膜区、基膜内皮下少量无特殊结构的电子致密物沉积;同时肾小球袢腔内CD68~+巨噬细胞胞质内见嗜伊红、嗜复红颗粒,为增生性肾小球肾炎伴单克隆IgG沉积(PGNMID)伴肾小球巨噬细胞及系膜细胞内异常内含物。经硼替佐米联合地塞米松化疗后临床部分缓解,8个月后重复肾活检示肾小球细胞增生较前减轻,IgG消失,κ轻链明显减弱,胞质内内含物几近消失。     

增生性肾小球肾炎伴微管状单克隆免疫球蛋白IgA-λ沉积

中年男性,反复发作双下肢出血性皮疹及尿检异常,首次肾活检为"肾小球系膜增生性病变伴IgA沉积",诊断为"过敏性紫癜性肾炎"。逐渐出现高血压、肾功能不全和贫血,IgA水平增高,血清免疫固定电泳见λ型IgA单克隆条带,血轻链κ/λ比例明显低下,骨髓流式细胞学检查见单克隆浆细胞株,冷球蛋白阴性。两次重复活检光镜均表现为膜增生样病变伴栓塞,免疫荧光单克隆IgA-λ沉积,电镜下肾小球系膜区、内皮下、袢腔内及浸润细胞胞质内较多特殊微管状结构物质沉积,上皮侧偶见同类物质。最终诊断为具有肾脏意义的单克隆免疫球蛋白病,增生性肾小球肾炎伴微管状单克隆免疫球蛋白沉积(IgA-λ型)。     

单克隆IgG沉积的增生性肾小球肾炎

目的:了解单克隆IgG沉积的增生性肾小球肾炎临床病理特点。方法:回顾性分析单克隆IgG沉积的增生性肾小球肾炎患者的临床病理资料。结果:9例患者中男性5例,女性4例,肾活检时平均年龄49.8±10.9岁,肾脏病病程15.9±13.1月;血清白蛋白29.0±5.5g/L,8例患者血清白蛋白降低,尿蛋白定量5.6±2.8g/d,7例伴镜下血尿,尿N-乙酰-β-D-氨基葡萄糖苷酶72.3±38.6U/(g·cr),尿视黄醇结合蛋白11.3±17.1mg/L,血清肌酐(SCr)209.5±176.8μmol/L,7例患者SCr升高。补体C3下降5例,补体C4均正常。高血压8例,贫血8例,浆细胞均未见异常,7例行血清免疫固定电泳仅1例存在血清异常IgGκ型条带。肾活检病理光镜为膜增生样病变,3例亦见肾小球结节,1例伴新月体。电镜下见肾小球基膜内皮下、系膜区及少量上皮侧颗粒状电子致密物,其中2例电子致密物呈晶格状结构。患者均有IgG和C3在肾小球内的沉积,5例伴C1q沉积。IgG3κ型3例,IgG3λ型3例,IgG1κ型2例,IgG1λ型1例。结论:单克隆IgG沉积的增生性肾小球肾炎以中老年多见,临床表现大量蛋白尿、血尿,多数患者肾功能不全和贫血,部分出现血清异常单克隆条带。组织学为肾小球膜增生样病变,肾小球见颗粒状电子致密物,少数呈晶格状结构,沉积物以IgG3亚型多见。     

伴微管状κ轻链沉积的增生性肾小球肾炎

中年男性患者,临床表现大量蛋白尿、镜下血尿,伴低白蛋白血症、急性肾损伤、高血压、贫血等。血免疫固定电泳示κ型Ig G单克隆免疫球蛋白条带。肾活检病理示肾小球膜增生性病变伴κ轻链沉积,电镜下观察肾小球毛细血管袢内皮下大量微管状结构,直径14～22 nm,最终诊断为伴微管状κ轻链沉积的增生性肾小球肾炎。     

1例单克隆IgG沉积的增生性肾小球肾炎临床分析

目的探讨单克隆IgG沉积的增生性肾小球肾炎（proliferative glomerulonephritis with monoclonal IgG deposits,PGNMID）的临床病理特点,加深对PGNMID的认识。方法分析1例PGNMID患者的临床病理特点,并对PGNMID相关文献进行复习。结果 PGNMID是一种少见疾病,以中、老年患者常见,主要临床表现包括蛋白尿、血尿,多数伴肾功能不全。肾活检病理组织学表现为肾小球增生性病变或膜增生样病变,免疫荧光检查肾小球内单克隆IgG沉积,电镜观察见沿肾小球毛细血管袢和（或）肾小管基膜外侧细沙样电子致密物沉积。结论老年肾病综合征或大量蛋白尿患者,尤其肾活检证实肾小球内单一免疫球蛋白IgG沉积者,应行IgG亚型染色及肾组织轻链染色,当电镜发现沿肾小球毛细血管袢特殊的电子致密物沉积时,应结合临床及实验室检查结果,诊断PGNMID,并寻找可能的病因,以提高PGNMID的诊断水平。     

伴单克隆免疫球蛋白IgA沉积的膜增生性肾小球肾炎

中年男性患者,反复发作双下肢皮肤紫癜16年,肾脏损害表现为肾病综合征,大量镜下血尿,血压及血清肌酐升高,轻度贫血。2009年曾行肾活检诊断为"过敏性紫癜性肾炎";2016年5月发现血M蛋白阳性(λ-IgA),重复肾活检为膜增生性肾小球肾炎,免疫荧光提示IgA++,轻链染色λ++、κ-,电镜下见晶格状电子致密物沉积;最终诊断为浆细胞病,伴单克隆λ-IgA沉积的膜增性肾小球肾炎,予沙利度胺治疗效果欠佳,硼替佐米治疗后病情好转。     

刚果红阳性的纤维性肾小球肾炎

青年女性,临床表现为水肿,大量蛋白尿、大量镜下血尿,低蛋白血症,血清肌酐升高,血压偏高。肾活检组织形态学改变为肾小球系膜区及血管袢较多PAS弱阳性、不嗜银的异常物质沉积,免疫荧光肾小球IgG多克隆及κ、λ轻链阳性,电镜下观察到肾小球系膜区大量、基膜内皮下和上皮侧少量直径为14～27 nm纤维丝状物质沉积,刚果红染色肾小球弱阳性,DNAJB9染色肾小球强阳性,最终诊断为刚果红阳性的纤维性肾小球肾炎。     

轻链足细胞病伴轻链肾小管病

老年女性患者,临床表现肾脏及血液系统为主的多系统损害,肾脏损害以中等量蛋白尿、低白蛋白血症为主要症状.肾外有轻度贫血及血小板减少,血清免疫固定电泳提示κ型IgG单克隆免疫球蛋白条带.肾活检组织学改变为肾小球足细胞及肾小管上皮细胞肿胀,胞质内见结晶样物质;免疫病理示κ轻链阳性,电镜下见菱形、圆形、梭形等多种形状的结晶,免疫胶体金技术证实上述结晶κ轻链阳性.该患者最终诊断为轻链足细胞病伴轻链肾小管病,考虑浆细胞异常增生性疾病所致.     

毛细血管袢腔内单克隆IgM沉积病

慢性肾脏病(CKD)老年男性患者,以少量蛋白尿,大量镜下血尿起病,CKD基础上出现急性肾损伤,肾外表现有脑梗塞,贫血,免疫固定电泳见IgMκ型单克隆免疫球蛋白条带,骨髓流式细胞检测提示克隆性浆细胞0.12%,血冷球蛋白阴性,冷凝集素试验阳性,低补体血症。肾活检病理示肾小球增生性病变,肾小球毛细血管袢腔内及肾间质小动脉管腔内较多PAS强阳性的栓塞,免疫荧光IgM-κ沉积,电镜下电子致密物无特殊超微结构。最终诊断为毛细血管袢腔内单克隆IgM沉积病。     

Fabry病合并IgA肾病

青年女性,慢性病程,临床表现少~中等量蛋白尿伴少量镜下血尿,肝肾功能正常,无肾外表现,无家族史。肾活检示肾小球系膜增生性病变伴足细胞胞质大量泡沫变性,免疫荧光染色IgA沉积于肾小球系膜区,甲苯胺蓝染色见肾小球足细胞胞质内大量嗜甲苯胺蓝颗粒,电镜观察除肾小球系膜区电子致密物沉积外,足细胞胞质内可见髓样小体及斑马小体。该患者最终诊断为Fabry病合并IgA肾病。     

Macrocytosis associated with monoclonal gammopathy

OBJECTIVE: To report the potential association between unexplained macrocytosis and monoclonal gammopathy. METHODS: We retrospectively reviewed the medical records of patients who had monoclonal protein detected by serum electrophoresis and immunofixation from October 1999 until September 2003 at our institution. Patients with concomitant macrocytosis were included in this study. We collected data on patient demographics, evaluations performed for macrocytosis, pertinent laboratory tests relevant to the diagnosis of monoclonal gammopathy and presence of associated hematologic disorders. RESULTS: We identified 258 patients with monoclonal gammopathy. Thirty-one (12%) of them had concomitant macrocytosis. Of the latter group, 14 (5%) patients had no identifiable cause of macrocytosis after thorough evaluation and were considered to have macrocytosis associated with monoclonal gammopathy. The median values for mean cell volume and serum monoclonal protein were 103.9 fL (range 100.8-109.8) and 1.95 gm/dL (range 0.8-4.3), respectively. Most patients had IgG (71%) and kappa light chain (79%). All of the 11 (of 14) patients who underwent a bone marrow biopsy as part of the initial evaluation had megaloblastoid maturation of the erythroid precursors. No correlation was found between the level of serum monoclonal protein and the degree of macrocytosis (r = +0.48, P = 0.08). After a median follow-up of 22.5 month (range 3-60+), all but one patient had persistent but stable macrocytosis. CONCLUSION: Macrocytosis can be a manifestation of monoclonal gammopathy. Disorders associated with monoclonal gammopathy should be considered in the differential diagnoses during evaluation of macrocytosis.     

Coincident multiple myeloma and non-Hodgkin's lymphoma with 2 serum monoclonal immunoglobulins

A case with features of both multiple myeloma and non-Hodgkin's lymphoma at the moment of diagnosis is presented. The patient had lytic bone lesions and biclonal gammopathy, IgM kappa and IgA kappa. In the bone marrow biopsy, there was a diffuse infiltration by atypical plasma cells coexisting with an interstitial and nodular infiltration by poorly differentiated lymphoid cells. Immunofluorescence studies showed positive staining with alpha and kappa antisera in the cytoplasm of plasma cells and with mu and kappa antisera on the surface of lymphoid cells. After the beginning of chemotherapy, the IgA kappa monoclonal protein disappeared and the IgM kappa monoclonal protein remained constant.     

A novel type of familial transthyretin amyloidosis, ATTR Asn124Ser, with co-localization of kappa light chains.

A 68-year-old Italian woman who had a clinical history of thyroidectomy in 2002 presented with slowly progressing renal insufficiency and non-nephrotic proteinurea in 2004. A renal biopsy showed the occurrence of amyloid; the thyroid biopsy previously taken also revealed amyloid infiltration. Other amyloid-containing tissues included bone marrow and heart. The plasma cell level in the bone marrow was found to be less than 5% and both serum and urine samples were positive for a monoclonal kappa light chain band. DNA analysis unexpectedly revealed the presence of a novel transthyretin (TTR) mutation, ATTR Asn124Ser. Histologically, amyloid deposits in the thyroid had a homogeneous appearance with moderate Congophilia. In immunohistochemistry, a kappa light chain antiserum showed positive immunoreactivity with amyloid deposits in the thyroid. Furthermore, a TTR antiserum, anti-TTR50-127, also recognized a number of amyloid deposits stained positive with the kappa light chain antiserum. Overall, the kappa light chain antiserum reacted with most of the amyloid deposits in the thyroid, whereas TTR immunoreactivity was scarcer, with a scattered appearance. In contrast, only the anti-TTR50-127 antiserum labeled amyloid in the kidney, albeit not all deposits. In this study, we report a patient having a novel TTR variant, ATTR Asn124Ser, with co-localization of kappa light chains in the amyloid deposits in the thyroid tissue.     

Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case

A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years.     

AA amyloidosis associated with morbid obesity (clinical case)

We present the case of a 45-year-old woman who was hospitalized due to severe macrocytic anemia and renal failure. The patient presented a morbid obesity.The immunological study showed anti-ENA anti-SSA (Ro52) positive, with negative antinuclear antibodies. Also in the proteinogram (serum immunofixation) the presence of monoclonal bands IgG lambda and IgG kappa, monoclonal component 7.2% (4.68 g/L), with elevation of free light chains (kappa 95.94 mg/L (3.3–19.4), evidenced, lambda 145.17 mg/L (5.71–26.3)).The bone marrow study showed an infiltration of 5% of plasma cells and positive for AA amyloid. Finally, a percutaneous renal biopsy was performed, which again showed amyloid infiltration.In the genetic study, 2 mutations of the family Mediterranean fever gene (MEFV) have been identified.Secondary AA amyloidosis has been described associated with obesity, in addition to a percentage of cases of unknown etiology.     

Multiple myeloma in a patient in remission from malignant lymphoma]

A 71-year-old man was admitted because of right cervical lymph node swelling in February 1986. Lymph node biopsy revealed that he suffered from diffuse, large cell malignant lymphoma. Immunological staining showed lymphoma characterized by B cell markers, IgG, kappa type. Bone marrow aspiration, revealed no evidence of lymphoma and 0.2% plasma cells. The clinical stage was IIA. The patient was treated with the CHOP regimen (doxorubicin, cyclophosphamide, vincristine and prednisolone), which achieved complete remission. In October 1988, he was re-admitted because of a subcutaneous abscess, and biopsy of the inguinal lymph node showed reactive lymphadenitis. Although he improved with antibiotic therapy, laboratory date on admission showed monoclonal gammopathy. Serum immunoelectrophoresis demonstrated a monoclonal bow of IgA kappa type, and bone marrow aspiration revealed hypercellularity with an increased number of plasma cells (76.8%). The patient was diagnosed as having multiple myeloma, and combination chemotherapy was begun. He now attends the out-patient department at our hospital. The development of multiple myeloma has not been reported previously during a course of malignant lymphoma. Although the association of these two B cell neoplasias was unknown, in this case both showed the characteristic of kappa type light chains. This case may provide information concerning tumor cell origin.     

Eosinophilic fibrohistiocytic lesion of bone marrow associated with monoclonal gammopathy and osteolytic lesions

We describe a 63-year-old male patient with severe osteoporosis, multiple lytic bone lesions, and monoclonal gammopathy (IgG lambda). Whereas the tentative diagnosis in this case was multiple myeloma, bone marrow trephine biopsies of the iliac crest and from an osteolytic lesion of the tibia both showed a peculiar infiltrate consisting of numerous elongated mast cells, eosinophils, and some plasma cells and lymphocytes. The bone marrow lesions fit the diagnosis of eosinophilic fibrohistiocytic lesion of bone marrow (EFHBM). The patient had no abnormality that could be related to a known allergic disease, and no relationship to drug hypersensitivity could be established. The features of the bone marrow infiltrate and its association with monoclonal gammopathy may suggest a linkage between EFHBM and the monoclonal gammopathy.     

A solitary plasmacytoma of donor origin arising 14 years after kidney allotransplantation

Summary Allotransplantation of solid organs transfers passenger leucocytes which may give rise to a state of persistent microchimaerism. In this report we describe the case of a patient who developed a solitary plasmacytoma in a transplanted kidney more than 10 years after allografting. The diagnosis was established on the basis of the presence of a monoclonal IgG kappa peak in the serum, and light chain proteinuria, the plasmacytoid features of tumour cells including cell surface expression of IgG, kappa light chains, CD20, CD38 and CD56, the absence of lytic bone lesions and a normal bone marrow biopsy, and the disappearance of the monoclonal IgG peak after graft nephrectomy. A donor origin of the tumour was established by HLA DNA typing of tumour, tumour-free kidney tissue, and peripheral blood leucocytes, respectively.     

Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology

Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density (P<0·001 respectively). ADC was significantly different between patients and controls (P<0·01) and before and after systemic therapy (P<0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden.     

Amyloid arthropathy resembling seronegative rheumatoid arthritis in a patient with IgD-kappa multiple myeloma

A 67-year-old woman suffered from symmetrical polyarthralgia and multiple joint swelling simulating rheumatoid arthritis (RA). Laboratory examination showed negative results for rheumatoid factor, decreased levels of IgG, IgA, and IgM, and an increased level of IgD. Immunoelectrophoresis in her serum and urine revealed an IgD-kappa monoclonal component and Bence Jones protein (kappa), respectively. A bone marrow biopsy showed an excess of atypical plasma cells. A synovial biopsy revealed amyloid deposition composed of IgD-kappa. She was diagnosed with amyloid arthropathy (AmyA) secondary to IgD-kappa multiple myeloma. It is important to pay attention to AmyA due to multiple myeloma in patients with seronegative RA.