Chronic sclerosing sialadenitis of the submandibular gland: an entity of IgG4-related sclerosing disease

Chronic sclerosing sialadenitis typically involves the submandibular gland. It usually occurs in the middle-aged and elderly adults with a slight male predominance. Recent evidences have suggested that it is an entity of IgG4-related sclerosing disease and has distinct histopathological features, such as a dense lymphoplasmacytic infiltrate, sclerosis and obliterative phlebitis. It is important to discriminate this entity from other diseases, trying to give effective treatment to the patients. In this report, we described a patient having chronic sclerosing sialadenitis in the submandibular gland.     

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.     

Lymphocyte subsets in irradiation-induced sialadenitis of the submandibular gland

AIMS: Irradiation-induced sialadenitis is a significant cause of morbidity in head and neck cancer patients receiving radiotherapy. Neither the exact aetiopathology of chronic irradiation-induced sialadenitis nor the mechanisms leading to atrophy of the glandular cells associated with an increase in extracellular matrix are understood. The aim of our study was to determine the phenotype of the inflammatory infiltrate and to study its distribution in the affected submandibular glands. METHODS AND RESULTS: Paraffin-embedded submandibular glands from a homogeneous group of 19 patients with advanced oropharyngeal cancer who received conventional radiotherapy to the primary site and upper neck were analysed. In all patients the radiation dose and field were approximately equal. The submandibular glands were obtained during neck dissection. To characterize the lymphoid infiltrate, all tissue sections were immunostained for T cells (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20), and macrophages (Ki-M1p). A histopathological classification into four grades was established based on the degree of glandular atrophy, fibrosis and lymphocytic infiltration. Phenotypic analysis of submandibular gland sections revealed that the great majority of lymphocytic infiltrates were cytotoxic T cells associated with acinar cell destruction. CONCLUSIONS: The significantly elevated frequencies of cytotoxic cells in the submandibular glands of patients with irradiation-induced sialadenitis suggest that cell-mediated immune mechanisms may play a part in the pathogenesis of this disease.     

A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis)

There is now increasing evidence that IgG4 is closely involved in idiopathic sclerosing lesions, such as sclerosing pancreatitis and sclerosing sialadenitis. In this report, we describe a case of IgG4-related retroperitoneal and mediastinal fibroses. A 52-year-old man presented with dull back pain and was found to have a continuously surrounding paraaortic mass. A biopsy specimen taken from the retroperitoneum showed a diffuse lymphoplasmacytic infiltration intermixed with fibrosis. Many IgG4-positive plasma cells were demonstrated on immunostaining. His serum IgG4 concentration was 392 mg/dL (reference range, <70). We treated this patient with a corticosteroid, which markedly diminished the paraaortic mass along with lowering of his serum IgG4 concentration. The possible involvement of IgG4 was suggested in the pathogeneses of retroperitoneal and mediastinal fibroses in this patient. IgG4 might be useful in the clinical management of retroperitoneal or mediastinal fibrosis to differentiate them from malignant tumors and predict steroid sensitivity.     

腹膜后纤维化的CT诊断

研究腹膜后纤维化的CT表现。分析经临床病理证实的9例腹膜后纤维化的CT表现,其中男性4例、女性5例,平均年龄53．7岁;特发性6例,继发性3例。9例均行CT平扫及增强检查。9例中CT平扫表现为腹膜后间隙或盆后间隙的低密度、不均匀密度或等密度弥漫性浸润病变4例,不规则肿块样病变5例,增强检查病变显示不同程度强化,多数病例伴有肾盂及输尿管扩张积水。因此,CT能很好显示腹膜后纤维化病变的各种表现,腹膜后间隙出现弥漫浸润性或不规则肿块样病变,并合并肾盂及输尿管扩张积水时应考虑到本病诊断。     

Chronic sclerosing sialadenitis of the submandibular gland is mainly due to a T lymphocyte immune reaction.

The aim of our study was to investigate the role of immunopathological processes in the pathogenesis of chronic sclerosing sialadenitis of submandibular glands (Küttner tumor). For this purpose, biopsy specimens from submandibular glands of 22 patients with the histological diagnosis of chronic sclerosing sialadenitis were analyzed. Paraffin-embedded tissues were immunostained for T-lymphocyte subsets (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20, Ki-B3), and macrophages (Ki-M1P). Polymerase chain reaction and capillary electrophoresis were used to detect rearrangements of the T-cell receptor gamma chain and the CDRIII region of the immunoglobulin heavy chain. In all cases, abundant cytotoxic T cells were found, especially in close association with ducts and acini. T-cell receptor gamma chain rearrangements showed a monoclonal pattern in 6 cases (27.3%), an oligoclonal pattern in 8 (36.4%), and a polyclonal pattern in 8 (36.4%). The B-cell reaction was less pronounced and largely restricted to lymph follicles. Molecular analysis of immunoglobulin heavy chain revealed a polyclonal rearrangement in 17 cases (77.3%). In conclusion, there is an intimate relationship between the T-cell-dominated inflammatory infiltrate and acinar and duct cells. This, together with the frequent demonstration of monoclonal and oligoclonal populations of cytotoxic T cells and their histopathological behavior, suggests that chronic sclerosing sialadenitis may be the result of an immune process triggered by intraductal agents.     

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis‐associated lung cancer (IPF‐LC). This study was performed to investigate the genomic profiles of IPF‐LC and to explore the possibility of defining potential therapeutic targets in IPF‐LC. We assessed genomic profiles of IPF‐LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice‐site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC‐related mutagenesis and the development of IPF‐LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF‐LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK–STAT signalling pathway were significantly amplified in IPF‐LC (P = 0.012). This study demonstrates that IPF‐LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

前列腺癌继发腹膜后纤维化1例

继发性腹膜后纤维化(RPF)以腹膜后包块为主要表现,发病率低,临床缺乏特征性表现,早期诊断困难,常致误诊误治。本报道继发于前列腺癌的RPF1例。继发于恶性肿瘤的RPF预后差,早期诊治尤为重要。     

IgG4-related sclerosing mesenteritis: a rare mesenteric disease of unknown etiology

Sclerosing mesenteritis is a rare inflammatory and fibrosing disorder of unknown etiology, while IgG4-related disease (IgG4-RD) consists of mass-forming, fibroinflammatory lesions characterized by high serum IgG4 levels and tissue infiltration of many IgG4-positive plasma cells; obliterative phlebitis is common. This report describes a case of sclerosing mesenteritis that was considered a manifestation of IgG4-RD. A 53-year-old man underwent right hemicolectomy because of an ileocecal mass that did not improve with conservative therapy. The ill-defined fibroinflammatory lesion extended in the mesentery with storiform fibrosis, obliterative phlebitis, and infiltration of many IgG4-positive plasma cells. The ratio of IgG4-positive/IgG-positive cells was 64%, and the ratio of forkhead box protein 3 (FOXP3)-positive/CD4-positive cells was elevated (13%). It is likely that at least some cases of sclerosing mesenteritis are a manifestation of IgG4-RD. It is important to investigate this relationship because steroid therapy may benefit such cases.     

Pathogenesis of idiopathic pulmonary fibrosis and its clinical implications

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of idiopathic interstitial pneumonia. The disease is thought to arise following an aberrant reparative response to recurrent alveolar epithelial cell injury leading to progressive loss of function. The median survival time is 3–5 years from diagnosis. Cigarette smoking, exposure to organic and inorganic dust and genetic factors have been shown to increase the risk of disease, although the cause of IPF remains elusive and its pathogenesis incompletely understood. In the last decade, several clinical trials evaluating novel therapies for IPF have been conducted but the results have been mostly disappointing. Conversely, compounds that target anti-fibrotic and growth factor pathways have been proven effective in slowing functional decline and disease progression. These promising results notwithstanding, truly effective therapeutic strategies will likely require combinations of drugs in order to target the multitude of pathways involved in disease pathogenesis.     

Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases

 

Aims:

Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed.  

Methods and results:

By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes.  

Conclusions:

Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.     

Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia

Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, Sawahata M & Ogura T
(2012) Histopathology
Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia Aims: To evaluate the histological characteristics differentiating chronic hypersensitivity pneumonitis (chronic HP) with a usual interstitial pneumonia (UIP)‐like pattern from idiopathic pulmonary fibrosis (IPF)/UIP. Methods and results: Surgical lung biopsy specimens from 22 patients with chronic HP diagnosed as having a UIP‐like pattern upon histological examination and 13 patients with IPF/UIP were examined and the incidences of bronchiolitis, perilobular fibrosis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, fibroblastic foci, honeycombing, granulomas, giant cells, lymphocytic alveolitis and lymphoid follicles were compared. Bronchiolitis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, granulomas, giant cells and lymphocytic alveolitis were significantly more frequent among patients with chronic HP than among patients with IPF (all P < 0.01). Conclusions: Centrilobular fibrosis, bridging fibrosis and organizing pneumonia, in addition to bronchiolitis, granulomas and giant cells, are characteristic features of chronic HP with a UIP‐like pattern. These features are therefore important in differentiating chronic HP from IPF/UIP, as management strategies differ for the two disorders.     

Chronic sialadenitis with psammoma bodies mimicking neoplasia in a fine-needle aspiration specimen from the submandibular gland

A 65-year-old woman with a submandibular gland nodule had a fine-needle aspiration specimen that contained groups of duct-type cells and a psammoma body, suggestive of adenocarcinoma. The resected gland showed chronic sialadenitis with sialolithiasis and psammoma bodies. In a series of 81 resected nonneoplastic submandibular glands from 72 patients, psammoma bodies, nonlaminated microcalcifications, or both were found in 46 (57%). They were located most commonly just outside of striated or intercalated ducts. When examining fine-needle aspiration specimens from the submandibular gland, it is important that one be aware that psammoma bodies may occur in normal, inflamed, irradiated, and neoplastic conditions.     

继发于恶性肿瘤的腹膜后纤维化临床和影像学特征分析

 摘要： 目的 探讨继发于恶性肿瘤的腹膜后纤维化（RPF, Retroperitoneal Fibrosis）的临床和影像学特征。 方法 分析我院1992年7月~2010年1月各科住院的RPF患者共106例,以其中继发于恶性肿瘤的8例RPF为研究对象,收集患者的临床资料并进行规律随访。 结果 8例恶性RPF中男性5例,女性3例,平均年龄59.6岁。原发肿瘤中生殖系统肿瘤4例,消化系统肿瘤2例,血液系统肿瘤及恶性神经鞘瘤各1例,其中1例同时患胃癌和膀胱癌。恶性RPF的临床症状与良性者比较并无特异,诊断主要依据影像学和病理。恶性RPF计算机X射线断层造影（CT）的特点：通常范围更广泛,肿物体积更大,包绕的腹主动脉、下腔静脉可发生背离脊柱方向的移位,输尿管可能发生向外侧移位;肿物边缘多呈结节或分叶状;肿物的中心多偏向髂血管方向。CT还可评价疗效和提示预后,病理学为最终确诊依据。 结论 恶性RPF临床症状无特异性,但影像学表现有一定特征,有鉴别诊断意义。     

特发性肺纤维化相关miRNAs的研究新进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种致死性的进行性间质性肺病,病因至今仍不明确,也缺乏有效的治疗方法.miRNAs研究涉及许多疾病的发生、诊断和治疗,现已发现多种miRNAs与特发性肺纤维化有密切的关系.本文将从促纤维化、抗纤维化以及临床诊断3方面来综述与特发性肺纤维化相关的新的miRNAs的研究状况,为早日揭示特发性肺纤维化的发病机制、发现有效的治疗措施提供科学资料.