Pulmonary inflammatory myofibroblastic tumor and IgG4-related inflammatory pseudotumor: a diagnostic dilemma

IgG4-related inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) share morphological features like a prominent fibroblastic/myofibroblastic proliferation and the presence of inflammatory cells. Since IPT is managed conservatively and IMT is treated by surgical excision, it is important to differentiate these two lesions. The aim of this study is to highlight morphological and immunohistochemical features that distinguish IPT and IMT. Clinicopathological characteristics of cases diagnosed as pulmonary IPT or IMT from 1997 to 2013 were reviewed. The histological features were studied on hematoxylin and eosin-stained sections. Immunohistochemistry was done for IgG, IgG4, ALK-1, SMA, desmin, and CD34 for classification into IPT and IMT. Of the ten patients, seven were male and the age ranged from 4 to 58 years. The tumor size ranged from 1.5 to 4.0 cm in diameter. Histologically, proliferation of bland-looking spindle cells along with fibrosis and an inflammatory infiltrate comprising of lymphocytes and plasma cells were the common morphological features of both lesions. The spindle cell proliferation was more marked in IMT whereas lymphoplasmacytic infiltrate was more prominent in IPT. Obstructive phlebitis was observed only in cases of IPT. IgG4 expression was noted in IPT, and the number of IgG4-positive plasma cells and the ratio of IgG4+/IgG+ plasma cells were significantly lower in IMT than in IgG4-related IPT. Expression of anaplastic lymphoma kinase (ALK) was observed only in IMT, but not in IgG4-related IPT. The proportion of proliferating spindle cells, lymphoplasmacytic infiltrate, obstructive phlebitis, IgG4+ plasma cells and the ratio of IgG4+/IgG+ plasma cells, and ALK expression are helpful in differentiating these morphologically similar but biologically different lesions, which require different treatment modalities.     

Inflammatory aortic aneurysm: possible manifestation of IgG4-related sclerosing disease

In this study, we investigate the hypothesis that IgG4-related autoimmune reaction is involved in the formation of inflammatory aortic aneurysms (IAA). We obtained 23 cases of IAA and 11 cases of atherosclerotic aortic aneurysms (AAA) as control group. We evaluated the expression of IgG4 in both IAA study cases and AAA control cases. In addition, immunohistochemical expression of C-Kit, CD21, CD34, S-100 protein, SMA, vimentin, p53, beta-catenin, and ALK-1, and EBV-LMP1 expression by in situ hybridization were performed only in IAA cases. Of the 23 patients, 20 were males and 3 were females (M: F ratio 6.7:1); age ranged from 43 to 81 years (average 64.3 years). Histologically, all 23 cases of IAA formed a mass that displayed inflammatory myofibroblastic tumor-like features. All lesions stained strongly and diffusely for vimentin and SMA (100%); 17 stained strongly and focally for CD34 (74%); and all were negative for C-Kit, CD21, S-100 protein, p53, beta-catenin, EBV-LMP1, and ALK-1. The numbers of infiltrating IgG4-positive plasma cells in IAA cases exceed that of AAA cases. Score 3 (>50 plasma cells/one 40X field) of IgG4-positive plasma cells was only seen in IAA cases (13/23, 57%), whereas none of the 11 cases of AAA showed score 3 IgG4-positive plasma cells (P=0.0018, Fischer‘s exact test). Our findings suggest that IAA may be an aortic manifestation of the IgG4-related sclerosing disease. The high number of positive plasma cells, >50 plasma cells/one 40X field is more specific for the IAA than for AAA; however, lesser number can be seen in both IAA and AAA patients.     

Calcifying fibrous tumour: An IgG4‐related disease or not?

Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4‐related diseases (IgG4‐RD). The possible role of IgG4‐positive plasma cells in calcifying fibrous tumour was investigated. The aim of this study was to determine any potential relationship between IgG4‐RD and CFT. Thirteen cases with a total of 16 CFTs were reviewed. Lesion samples were immunostained with anti‐IgG4 and anti‐IgG antibodies. The number of IgG4‐positive and IgG‐positive plasma cells (IgG + PC) and their ratios were estimated. Plasma cells were found in all tumours. IgG4‐positive plasma cells ranged from 0 to 71 per high‐power field (HPF; mean 17.8/HPF), and IgG + PC ranged from 2 to 93/HPF (mean 42.6/HPF). The IgG4/IgG ratio ranged from 0% to 80% (mean 29%). There were seven tumours with the ratio of IgG4/IgG + PC that exceeded 40%. Various degrees of stromal fibrosis were present in eight tumours. All tumours have variable calcification. The histopathological features of CFT were found to be similar to those of IgG4‐RD. Some CFT also showed a high number of IgG4‐positive plasma cells, and the ratio of IgG4/IgG + PC exceeded 40%, most notably in patients with concomitant inflammatory or autoimmune disease. The long‐term follow‐up showed no evidence of IgG4‐RD in any of these patients. Our findings suggest that while CFT overlaps morphologically with IgG4‐RD, it probably should not be classified as an IgG4‐RD.     

IgG4-related kidney disease

IgG4-related disease (IgG4-RD) is a recently recognized systemic immune-mediated disease that can affect nearly any organ or tissue. The most common manifestation in the kidney is IgG4-related tubulointerstitial nephritis (IgG4-TIN), which can present as renal insufficiency, renal mass lesions, or both. Histologically, IgG4-TIN is a plasma cell-rich interstitial inflammatory infiltrate with mononuclear cells, eosinophils, and increased IgG4+ plasma cells, along with expansile interstitial fibrosis that often has a “storiform” appearance. Tubular basement membrane immune complex deposits, best visualized on immunofluorescence staining, are present in most cases. IgG4-TIN usually shows a rapid response to steroid therapy. Glomeruli may be affected by IgG4-RD, usually in the form of membranous glomerulonephritis; other glomerular lesions have also been described. This review describes the different histopathologic patterns of renal involvement by IgG4-RD, with associated clinical, radiographic, and serologic features.     

IgG4-related disease of the ureter: report of two cases and review of the literature

IgG4-related disease (IgG4-RD) is a recently recognized multi-organ fibro-inflammatory lesion characterized by elevated IgG4 serum levels and mass-forming lesions. This condition shows similar histological features independently of the site of origin including storiform fibrosis, obliterative phlebitis, and dense lymphoplasmacytic infiltrate with a conspicuous IgG4-positive plasma cell component. Since this disease has only recently been categorized as a single specific nosologic entity, lesions with these typical morphological features have previously been named in different ways, creating some confusion and making it difficult to identify cases published in the literature. Lesions with features suggesting IgG4-RDs have very rarely been reported in the ureter, and they have been named using the terms “inflammatory pseudotumor” and “idiopathic segmental ureteritis.” Herein, we describe the clinicopathological features of ureteral IgG4-RD found in two different patients. An 82-year-old female and a 77-year-old male underwent ureteral resection due to severe ureteral wall thickness and lumen stenosis suggestive of urothelial carcinoma. However, histological examinations showed transmural fibro-inflammatory lesions, with abundant IgG4 plasma cells intermixed with histiocytes, lymphocytes, fibroblasts, and scattered eosinophils. We have also accurately reviewed the literature in order to identify, among lesions diagnosed with different names, examples of ureteral IgG4-related lesions to give the reader a comprehensive overview of this relatively rare inflammatory disease. We suggest using the name “ureteral IgG4-RD” for those lesions showing the same morphological features as IgG4-RDs located elsewhere.     

Immunohistochemical characterization of oral mucosal lesions in cats with chronic gingivostomatitis

Histological and immunohistochemical studies were performed on samples of the glossopalatine mucosa from 30 cats with feline chronic gingivostomatitis (FCGS). Immunohistochemical labelling and computer-assisted morphometric analysis were used to identify expression of CD3, CD4, CD8, CD79a, IgG, IgM, IgA, leucocyte antigen 1 (L1) and class II molecules of the major histocompatibility complex (MHC) in tissue sections. Mast cells were detected by toluidine blue staining. The microscopical lesions were graded by severity of inflammation and although this grading correlated significantly with the severity of mucosal inflammation assessed at clinical examination, sites assessed as clinically normal or mildly inflamed were poorly predictive of the histopathological grade in the corresponding tissue sample. The number of CD79a+ cells (mostly plasma cells), L1+ cells (mostly neutrophils) and CD3+ T cells, and the level of MHC class II expression, tended to correlate with the severity of the inflammation. In general, CD8+ T cells were more numerous than CD4+ T cells. The majority of the plasma cells were of the IgG isotype and fewer IgA+ and IgM+ plasma cells were present. In some cases MHC class II expression by mucosal epithelium, salivary duct epithelium or skeletal muscle fibres was observed. Relative to equivalent oral mucosal samples from healthy cats, the number of cells labelled for CD3, CD4, CD8, CD79a, IgG, IgM, IgA or L1, and the number of mast cells, within the lamina propria/submucosa were significantly increased. Limited analysis of the epithelial compartment also found more CD3+ T cells compared with healthy cats. These findings indicate that the glossopalatine mucosal lesions in FCGS represent a complex, chronic and destructive inflammatory process affecting the epithelium and lamina propria, with frequent extension into submucosal tissues. The predominance of CD8+ cells over CD4+ cells suggests the induction of an underlying cytotoxic cell-mediated immune response, which could be consistent with a viral aetiology.     

IgG4 plasma cell myeloma: Clinicopathological characteristics and diagnosis

Plasma cell myeloma (PCM) is usually associated with the presence of M‐protein in the serum and urine of patients, and about half of the PCM cases exhibit the IgG M‐protein and increased gamma‐globulin fraction on membrane electrophoresis. The IgG4 subclass is located in the beta‐2 fraction on membrane electrophoresis. The aim of this study was to develop a method to evaluate IgG4‐producing PCM (IgG4‐PCM) and its clinicopathological characteristics. We found three cases of IgG4‐PCM among 80 cases of IgG‐producing PCM by membrane electrophoresis, which were confirmed by IgG4 immunostaining. None of the cases had a clinical history of IgG4‐related disease, although they exhibited high levels of serum IgG4. A bone marrow aspiration specimen had an increased number of plasma cells with a relatively mature morphology. No cases exhibited lymphoplasmacytic inflammation, obliterative phlebitis or fibrosis. Immunohistochemistry revealed that tumor cells expressed CD138 and IgG4 and showed monoclonal expression of kappa. We revealed that IgG4‐PCM might not be associated with IgG4‐related disease and that the detection of M‐protein with beta‐globulin fraction by electrophoresis may be useful for screening IgG4‐PCM.     

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe

Laco J, Ryska A, Celakovsky P, Dolezalova H, Mottl R & Tucek L (2011) Histopathology 58 , 1157–1163 Chronic sclerosing sialadenitis as one of the immunoglobulin G4‐related diseases: a clinicopathological study of six cases from Central Europe Aims: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4‐related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. Methods and results: Our CSS series included four females and two males, aged 32–76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS‐cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG‐positive plasma cells per high‐power field (HPF) was 157; median number of IgG4‐positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. Conclusions: This is the first European series to demonstrate that CSS belongs to the family of IgG4‐related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4‐positive plasma cells, and should be regarded as a member of the IgG4‐related disease group.     

Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease.

Recently, much attention has focused on IgG4-related disease, which is characterized by abundant IgG4-positive plasma cell infiltration and high serum IgG4 levels. IgG4-related disease sometimes manifests as tumorous lesions, and its relationship to inflammatory pseudotumor has been suggested. In this study, we examined clinicopathological features of a total of 16 cases of hepatic inflammatory pseudotumor (11 men and 5 women with an average age of 67 years) with respect to IgG4-related disease. The tumors could be pathologically classified into two types: fibrohistiocytic (10 cases) and lymphoplasmacytic (6 cases). Fibrohistiocytic inflammatory pseudotumors were characterized by xanthogranulomatous inflammation, multinucleated giant cells, and neutrophilic infiltration, and mostly occurred in the peripheral hepatic parenchyma as mass-forming lesions. In contrast, lymphoplasmacytic inflammatory pseudotumors showed diffuse lymphoplasmacytic infiltration and prominent eosinophilic infiltration, and were all found around the hepatic hilum. In addition, venous occlusion with little inflammation and cholangitis without periductal fibrosis were frequently observed in the fibrohistiocytic type, whereas obliterative phlebitis and cholangitis with periductal fibrosis were common features of the lymphoplasmacytic type. Interestingly, IgG4-positive plasma cells were significantly more numerous in the lymphoplasmacytic than fibrohistiocytic type. However, two of the fibrohistiocytic inflammatory pseudotumors had relatively many IgG4-positive plasma cells. In conclusion, hepatic inflammatory pseudotumor could be classified into two types based on clinicopathological characteristics. The lymphoplasmacytic type is unique, and could belong to the so-called IgG4-related diseases. In contrast, the fibrohistiocytic type might still be a heterogeneous group of disorders. This latter type seems pathologically different from IgG4-related disease, although cases with relatively abundant IgG4-positive plasma cells should be differentiated from IgG4-related disease with secondary histopathologic modifications.     

Ocular adnexal IgG4-related disease: comparative analysis with mucosa-associated lymphoid tissue lymphoma and other chronic inflammatory conditions

Go H, Kim J E, Kim Y A, Chung H K, Khwarg S I, Kim C‐W & Jeon Y K
(2012) Histopathology  60, 296–312
Ocular adnexal IgG4‐related disease: comparative analysis with mucosa‐associated lymphoid tissue lymphoma and other chronic inflammatory conditions Aims: Making a differential diagnosis of IgG4‐related disease from mucosa‐associated lymphoid tissue (MALT) lymphoma or any other chronic inflammation is often challenging. Moreover, the association with secondary lymphoma of ocular adnexal IgG4‐related disease needs to be elucidated. Methods and results: We investigated 14 cases of IgG4‐related disease, nine MALT lymphomas and 12 other chronic inflammations involving the lacrimal gland and orbit. Bilateral involvement was frequent in IgG4‐related diseases. The number of IgG4‐positive cells and the ratio of IgG4/IgG‐positive cells were higher in patients with IgG4‐related disease than in those with MALT lymphoma (P = 0.016; P < 0.001) and other types of inflammation (P < 0.001; P < 0.001). Monoclonal B cell proliferation was suspected in two cases (14.3%) of IgG4‐related disease. One of these patients also displayed monomorphous features suggesting secondary MALT lymphoma. In the other case, κ‐chain restriction in IgG4‐positive cells was observed, raising the possibility of IgG4‐producing MALT lymphoma. Trisomy 3, trisomy 18 or MALT1 translocation was observed in none of the IgG4‐related cases. Regulatory T‐cell infiltration was higher in cases of IgG4‐related disease than in MALT lymphomas (P < 0.001) and other types of inflammation (P = 0.006). Conclusions: Some genetically and morphologically complicated cases of ocular adnexal IgG4‐related disease emphasize the need for in‐depth studies to differentiate this disease from MALT lymphoma, and to exclude secondary lymphoma.     

Inflammation of colon adenoma in the setting of type 1 autoimmune pancreatitis

Although immunoglobulin G4‐related diseases (IgG4‐RD) have been found to affect many organs, little is known about their effects on the colonic mucosae. Pathological examination of colon adenomas has shown inflammatory cell infiltration into the stroma. We therefore assessed the clinicopathological characteristics of colon adenomas in patients with type 1 autoimmune pancreatitis (AIP‐1), a representative IgG4‐RD. Both colon adenomas from patients with (IgG4 adenomas) and without (Non‐IgG4 adenomas) IgG4‐RD were characterized by moderate to severe lymphoplasmacytic and eosinophilic inflammation without fibrosis or phlebitis. The ratio of IgG4‐positive to IgG‐positive plasma cells (IgG4/IgG ratio) and the numbers of IgG4‐positive plasma cells were significantly higher in IgG4 adenomas than in Non‐IgG4 adenomas. IgG4‐positive plasma cells tended to be distributed diffusely in lower areas of the mucosae in IgG4 adenomas. We were unable to confirm whether IgG4 adenomas constituted an IgG4‐RD. However, IgG4 adenomas in the setting of IgG4‐RD may provide useful pathological information, supplementing a diagnosis of IgG4‐RD outside the colon, or may facilitate examination for IgG4‐RD, especially AIP‐1. IgG4 adenomas warrant further investigation.     

Immunohistochemical study of the inflammatory infiltrate associated with equine squamous cell carcinoma.

The distribution of T (CD3), B (CD79) lymphocytes, immunoglobulin (IgG, IgM and IgA)-producing plasma cells, macrophages (lysozyme, Mac387) and MHC Class II antigen was analysed in the inflammatory infiltrate associated with 19 equine squamous cell carcinomas (SCCs) and six cases of precancerous lesions (actinic keratosis). The SCCs came from the penis (11 cases), conjunctiva (four), skin (two), nasal cavity (one) and oral cavity (one). Seven cases were well-differentiated and 12 moderately differentiated. Nine cases showed no invasion of peritumoral deep tissues (locally invasive), whereas the remaining 10 cases were highly invasive. An abundant inflammatory infiltrate was associated with the majority of the SCCs and with lesions of actinic keratosis. This infiltrate was composed mainly of CD3(+)T lymphocytes, CD79(+)B cells and numerous IgG(+)plasma cells; IgM- and IgA-producing plasma cells were scarce and variable, respectively. Macrophages were usually numerous. Macrophages, lymphocytes, intra-epithelial dendritic cells and fibroblasts expressed MHC Class II antigen. No significant correlation was found between the nature of the inflammatory infiltrate and the SCC histological grade or degree of invasion, suggesting that the local anti-tumour immune response failed to prevent tumour invasion or metastasis. MHC Class II was expressed by a variable number of neoplastic epithelial cells in four SCCs, all of which were only locally invasive. In addition, in areas where SCC cells expressed Class II antigen, numerous CD3(+)T lymphocytes were present and some of them were associated with degenerate tumour cells. These findings suggest that the expression of MHC Class II by neoplastic cells induces an improved local anti-tumour immune response.     

Inflammatory pseudotumor‐like follicular dendritic cell sarcoma of the spleen: A report of six cases with increased IgG4‐positive plasma cells

Inflammatory pseudotumor (IPT)‐like follicular dendritic cell (FDC) sarcoma is a rare neoplasm typically occurring in the spleen or liver. We present six cases of EBV⁺ IPT‐like FDC sarcoma of the spleen among Koreans along with their clinicopathologic features and IHC results. Most patients presented with an asymptomatic, incidentally detected single splenic mass and were successfully managed by splenectomy alone. Concomitant disease was found in one case, showing EBV⁺ gastric carcinoma with lymphoid‐rich stroma. Histologic features showed fibro‐inflammatory lesions that were often accompanied by necrosis and epithelioid histiocytic collection, which are barely distinguishable from IPT. Tumor cells did not frequently express conventional FDC markers, including CD21 (3/6 positive cases), clusterin (4/6), and D2‐40 (2/6), but showed uniform positivity for smooth muscle actin (SMA). Noticeably, significant numbers of IgG4⁺ plasma cells were found within all six tumors. We suggest that the diagnosis of IPT‐like FDC sarcoma should be made by the application of a panel of FDC markers, and CD21 negativity or SMA positivity cannot be the criterion for exclusion of IPT‐like FDC sarcoma. Relationship of IPT‐like FDC sarcoma of the spleen and IgG4‐related sclerosing disease should be investigated in further studies.     

Sclerosing mesenteritis: A real manifestation or histological mimic of IgG4‐related disease?

We present three cases of sclerosing mesenteritis and review the literature to learn whether or not sclerosing mesenteritis is an IgG4‐related disease (IgG4‐RD). Our patients were all adult males. Their mesenteric masses ranged from 6.5 to 14.5 cm in the greatest diameter. Tissue specimens showed moderate to severe lymphoplasmacytic infiltration with occasional eosinophils against a background of irregular fibrosis. Both obliterative phlebitis and storiform fibrosis were noted in all cases. IgG4+ plasma cells were moderately increased in number (46 to 85 cells/high‐power field). However, unlike IgG4‐RD, the IgG4+/IgG+ plasma cell ratio was <40% (28% to 35%). Serum IgG4 concentrations were also within the normal range (43.2 to 105 mg/dL; normal range <135 mg/dL). Two biopsy cases showed spontaneous regression on imaging approximately 5 months later. No sclerosing conditions were found in other organs. The literature review identified 11 additional cases of sclerosing mesenteritis with IgG4+ plasma cell infiltration. However, conclusive cases with four characteristic features (high serum IgG4 levels, tissue IgG4 elevation, multi‐organ involvement, and effective response to glucocorticoid therapy) have never been reported. In conclusion, although sclerosing mesenteritis shares histological features with IgG4‐RD, most cases are less likely to be IgG4‐related. IgG4‐RD seemingly seldom, if ever, affects this anatomical site.     

Isolated thoracic aortitis: clinicopathological and immunohistochemical study of 11 cases

Isolated thoracic aortitis (ITA) is diagnosed in a variable proportion of patients operated on for dilation/aneurysm of ascending aorta. The etiopathogenesis of ITA remains unclear.We studied 11 cases of ITA in order to determine the role of IgG4-mediated immune responses in its pathogenesis.The series included nine women and two men aged 52–79 years. All patients developed aortic incompetence due to dilation/aneurysm of ascending aorta. None of the patients had a history of IgG4-related disease neither did they develop features of such disease during the follow-up period. The microscopic findings included the presence of lymphoplasmacellular fibrosing infiltrate of varied intensity involving the adventitia and media of aorta. This inflammation was associated with severe medial elastic fiber defects. Obliterative phlebitis of the vasa vasorum was absent. Immunohistochemically, the inflammatory infiltrate comprised T- and B-lymphocytes as well as plasma cells. The plasma cell population was polyclonal with a predominance of IgG-producing cells. In all the cases, IgG4-producing plasma cells were detected. In five cases, the count exceeded 20 cells per high-power field. The IgG4/IgG ratio ranged from 0.07 to 0.98 (median 0.55). In six cases with the ratio >0.50, severe adventitial fibrosis was present.To the best of our knowledge, ours is the first study focused on investigating the role of IgG4-positive plasma cells in the development of ITA. Our results suggest that a subset of ITA may represent aortic manifestation of IgG4-related disease. Further research is necessary in order to clarify this issue.     

钙化性纤维性肿瘤的临床病理学研究及其组织学发生的再评价

目的探讨钙化性纤维性肿瘤(CFT)的临床病理学特征及其组织学发生机制。方法对11例CFT的临床表现、组织学形态及免疫组织化学表型进行分析。结果11例CFT中男性5例,女性6例,年龄从25至52岁,平均38岁,位于盆腹腔6例、皮下软组织4例、阴囊内1例。临床上表现为缓慢增大的无痛性肿块,5例伴随其他病症或既往有炎性改变、外伤或手术史,4例病变为偶然发现,肿瘤多为单发,切除后未见复发。影像学显示病变为孤立性或多发性实性软组织肿块,境界清楚无包膜,实质内散在大小不等、数量不一的高密度钙化灶。大体上,肿瘤呈灰黄色,质硬,边清,圆形、卵圆形、分叶状或不规则形,最大径为0.5 ～20.0 cm,切面散在浅黄色斑点状钙化灶,切开时具有沙砾感。显微镜下显示肿瘤实质主要由玻璃样变的胶原纤维及厚壁血管构成,其中散在少量梭形细胞、单核炎性细胞、沙砾体及营养不良性钙化。此外,少数肿瘤边缘区局灶性中性粒细胞呈带状浸润,另见少量神经束及脂肪组织内陷。不同病例肿瘤实质外周区局灶性具有类似于孤立性纤维瘤、纤维瘤病、瘢痕疙瘩及炎性肌纤维母细胞瘤样形态学改变。沙砾体及营养不良性钙化分别形成于透明变性的血管及玻璃样变的胶原纤维。肿瘤组织内浸润的单核炎性细胞主要为淋巴浆细胞,局部区域可形成淋巴滤泡样结构。免疫组织化学染色显示所有受检的肿瘤组织内梭形细胞弥漫性表达波形蛋白,少数局灶性表达CD34、第八因子相关抗原及β-caltenin,其他标记为阴性。具有特征性的是,与炎性病变相比,CFT组织中浸润的浆细胞显著表达IgG及IgG4,且IgG4+/IgG+＞50％,IgG1及IgG3表达的细胞较少。结论CFT具有较为特征性的组织病理学表现,但其发病机制尚未明确。由于CFT与IgG4相关的硬化性疾病具有相似的组织学及免疫组织化学表型,因此,推测CFT可能为IgG4相关的硬化性疾病家族谱系中一种新的独立实体。该病变的发展呈良性经过,炎性改变及创伤可能为该病变的重要诱因,手术切除后罕见复发。     

Endometrial glandular and stromal breakdown,Part 3: Cytomorphology of “condensed cluster of stromal cells”

The aim of this study was undertaken to clarify the cytological characteristic of the “condensed clusters of stromal cells,” which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases. The material consists of 60 cases of cytologic smears for which histopathological diagnosis was obtained by endometrial curettage; they comprised 30 cases of EGBD and 30 cases of endometrioid adenocarcinoma grade 1 (G1). The following parameters were examined for “condensed clusters of stromal cells” in EGBD and for “clumps of cancer cells” in G1, respectively: (1) the occurrence of “condensed clusters of stromal cells”; (2) the nuclear shape; (3) a longer/shorter axis ratio in cell nuclei; (4) the area of cell nuclei; (5) the presence of overlapping nuclei; (6) nuclear crowding; (7) immunostaining. (1) “Condensed clusters of stromal cells” were only observed in EGBD. (2) A reniform nuclear shape was observed in 100% EGBD (P < 0.0001) in comparison to G1 (3%). (3) The longer/shorter axis ratio in cell nuclei, G1 (1.37 ± 0.2) was significantly lower in comparison to EGBD (1.53 ± 0.12, P = 0.0005). (4) Nuclear area in G1 (51.6 ± 11.9, P < 0.0001) was significantly higher in comparison to EGBD (24.3 ± 3.9 μm²). (5) The score of overlapping nuclei in EGBD (2.5 ± 0.49) was significantly higher in comparison to G1 (1.8 ± 0.44, P < 0.0001). (6) The nuclear crowding score was the same both in EGBD (2) and G1 (2) and these findings were not statistically significant. (7) Both CD10 and Wilms' tumor protein 1 were positive in the “condensed clusters of stromal cells” in the EGBD. The anti‐cytokeratin staining was positive in “clumps of cancer cells” in the G1. The evaluation of the immunocytochemical findings by combining the Wilms' tumor 1 protein, CD10, and the anti‐cytokeratin with the considered cytomorphologic features (reniform nucleus) may be useful for a correct diagnosis of EGBD in endometrial cytology. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Atypical squamous cells,cannot exclude high‐grade squamous intraepithelial lesion: Diagnostic features in surepath™ cervical samples

This study was undertaken to identify the situations in which a diagnosis of “Atypical squamous cells, cannot exclude a high‐grade squamous intraepithelial lesion (ASC‐H)” is offered in SurePath? cervical samples and to identify cytological criteria helpful in predicting high‐grade disease. 2,335 (3.4%) SurePath samples reported as atypical squamous cells (ASC) over a period of 2 years, including 1,112 cases with known hrHPV status were retrieved. 105/1,112 cases were categorized into ASC‐H, and slides were available for review in 88/105 cases. These 88 samples were divided into two categories based on follow‐up histological outcome and hrHPV status–category A: cases with CIN2+ lesions on follow‐up (n = 48) and category B: cases with ≤CIN1 lesions or hrHPV negative status (n = 40). 78% (82/105) cases of ASC‐H tested positive for hrHPV. Overall CIN2+ lesions were found in 50.3% (53/105) cases. Of 88 cases reviewed, HCGs were noted in 56.3% (27/48) cases in category A and 75% (30/40) cases in category B. Dispersed metaplastic cells and scattered small atypical cells were seen in 37.5% (18/48) cases in category A and 12.5%(5/40) in category B. The majority of cases with dispersed atypical cells had <20 cells/sample and cases with HCGs had <10 HCGs per sample. The majority of the cases reported as ASC‐H contained HCGs. Of these groups with nuclear crowding, disorganization and those with steep edges (“blocks”) are likely to predict high‐grade disease. The samples with only dispersed atypical cells had <20 cells/sample in majority of cases. In these, a disproportionate andespecially high nuclear: cytoplasmic ratio and irregular chromatin were the most useful features in predicting high‐grade disease. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Hyper-IgG4 disease: report and characterisation of a new disease

Background

We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis.

Methods

We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis.

Results

Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment.

Conclusion

We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good.