IgG4-related disease: an analysis of the clinicopathological spectrum: UK centre experience.

AIM: To retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD). METHODS: Winpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups-highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database. RESULTS: The study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD. CONCLUSION: Histological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.

Descriptive analysis of incidental and operable gallbladder carcinoma cases: a UK centre experience.

Objective: To identify and compare significant or relevant prognostic factors in pre-operatively diagnosed, surgically resectable, gallbladder cancer and in incidentally detected gallbladder cancer cases. Material and methods: Gallbladder resections (October 2009-March 2016) were identified on the histopathology Winpath database. Cases with a final histological diagnosis of gallbladder cancer (GBC) were categorised into: Group A: clinically suspected operable GBC (n = 13). Group B: incidental GBC with staged liver bed resection (n = 5). Group C: incidental GBC without staged liver bed resection (n = 15). The clinicopathological features were analysed in each group separately. Results: The overall incidence of primary (GBC) was 0.66% and all the cases were adenocarcinomas, of which, 6 of 33 (18.2%) were grade 1 and 15 of 33 (45.4%) were grade 3. Male to female ratio is 1:2.3. Of the 33 patients with GBC 14 (42.4%) has died of disease at 18-month follow-up. 15 of 33 had perineural invasion and 10/21 (47.6%) cases showed lymph node matastasis. Six cases had positive surgical margin and 9/15 showed direct liver invasion. Higher stage disease (T3/T4) was seen in 10/14 cases. Conclusion: The prognosis of primary GBC is poor and best clinical outcomes can be achieved with early diagnosis followed by radical cholecystectomy and staged liver resection with negative margins.

Mucinous Epithelium in Endometrial Curetting Leading to Diagnostic Conundrum: A Case Report.

Mucinous differentiation of the endometrium can occur in a spectrum of changes ranging from benign (metaplasia) to malignant (adenocarcinomas with mucinous differentiation). A rarer differential which is usually not considered is a teratoma. We present a case of a 55-yr-old woman with history of irregular perimenopausal bleeding. Endometrial curetting revealed proliferative mucinous epithelium on histology raising a possibility of low-grade epithelial mucinous malignancy. Hysterectomy was performed and histologic examination revealed a diagnosis of uterine mature teratoma. Mature cystic teratoma of the lower uterine segment is very rare and presence of just one element such as mucinous epithelium can lead to a misdiagnosis of carcinoma on biopsy or curetting.

Sarcomatoid Carcinoma Arising in a Gastric Duplication Cyst.

Malignancy arising within a gastric duplication cyst (GDC) is extremely rare; only 15 cases have been reported in the literature. We present a 70-year-old woman who was referred with a history of vague postprandial abdominal discomfort. Subsequent imaging identified a gastric cystic mass. A laparoscopic sleeve gastrectomy of a 90 × 60 × 60-mm cystic mass was performed. Histopathological examination showed the presence of a sarcomatoid carcinoma arising within a GDC. The patient, unfortunately, died 5 months after surgery with metastatic disease. To the best of our knowledge, this is the first case of sarcomatoid carcinoma arising within a GDC.

The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers.

Pancreatic Ductal Adenocarcinoma (PDAC) and biliary-tract cancers (BTC) often present at a late stage, and consequently patients have poor survival-outcomes. Circular RNAs (circRNAs) are non-coding RNA molecules whose role in tumourigenesis has recently been realised. They are stable, conserved and abundant, with tissue-specific expression profiles. Therefore, significant interest has arisen in their use as potential biomarkers for PDAC and BTC. High-throughput methods and more advanced bioinformatic techniques have enabled better profiling and progressed our understanding of how circRNAs may function in the competing endogenous RNA (ceRNA) network to influence the transcriptome in these cancers. Therefore, the aim of this systematic review was to describe the roles of circRNAs in PDAC and BTC, their potential as biomarkers, and their function in the wider ceRNA network in regulating microRNAs and the transcriptome. Medline, Embase, Scopus and PubMed were systematically reviewed to identify all the studies addressing circRNAs in PDAC and BTC. A total of 32 articles were included: 22 considering PDAC, 7 for Cholangiocarcinoma (CCA) and 3 for Gallbladder Cancer (GBC). There were no studies investigating Ampullary Cancer. Dysregulated circRNA expression was associated with features of malignancy in vitro, in vivo, and ex vivo. Overall, there have been very few PDAC and BTC tissues profiled for circRNA signatures. Therefore, whilst the current studies have demonstrated some of their functions in these cancers, further work is required to elucidate their potential role as cancer biomarkers in tissue, biofluids and biopsies.

Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm.

Gall bladder malignancy: an unusual association.

Gall bladder malignancy predominantly comprises adenocarcinoma and is found mostly in a late stage whereas primary lymphoma of mucosa associated lymphoid tissue (MALT) within the gall bladder is exceedingly rare and has an incidental presentation. We report a case of well differentiated adenocarcinoma with MALT lymphoma of the gall bladder in an 83 year old woman. To our knowledge, this is the first case of a carcinoma and lymphoma occurring simultaneously in the gall bladder.

Cardiac sarcoidosis and sudden death. The heart may look normal or mimic other cardiomyopathies.

Cardiac sarcoidosis has been known to give rise to heart failure, arrhythmias and sudden cardiac death. We have a large database of sudden cardiac death cases at the CRY Centre for Cardiac Pathology at Imperial College, London, UK in which we found 17 of 1,720 cases with a diagnosis of cardiac sarcoid. Macroscopic examination showed a variety of findings including left ventricular hypertrophy, a dilated thin-walled left ventricle, areas of fibrosis, changes resembling arrhythmogenic right ventricular cardiomyopathy and in some cases, no gross abnormalities. Histological examination revealed large areas of fibrosis and focal lymphocytic inflammation mimicking infarction/myocarditis. Careful search had to be made for non-necrotizing granulomata, since the lymphocytic foci, fibrosis and granulation tissue often predominated throughout the heart. The conduction tissue is often not sampled at autopsy despite the history of heart block. The heterogeneous nature of the macroscopic appearance and histological findings means that widespread sampling of the heart and the conduction system is essential in cases of sudden death in order that a diagnosis of myocardial sarcoidosis is not missed.

Incidental presentation of gall bladder MALT lymphoma.

BACKGROUND: Primary lymphomas of mucosa associated lymphoid tissue (MALT) within the gall bladder are exceedingly rare and may have an incidental presentation. CASE REPORT: We report a case of gall bladder MALT lymphoma diagnosed after cholecystectomy in a 65-year old woman. CONCLUSION: Normally the gall bladder is devoid of lymphoid tissue; however, it has been suggested that MALT lymphomas may occur secondary to chronic cholecystitis with cholelithiasis or bacterial infection based on similar mechanism as described previously in the stomach and conjunctiva. Surgical resection is considered curative if the disease is localised only to the gall bladder.

Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 51 cases in a tertiary cancer center.

OBJECTIVE: To analyze the importance of unique cytoarchitectural patterns and the immunohistochemical profile in the diagnosis of myoepithelial carcinomas. DESIGN: Retrospective case analysis. SETTING: Tertiary cancer center. PATIENTS: A total of 51 patients with myoepithelial-rich carcinomas diagnosed over a 14-year period were studied for demographic data and tumor histologic characteristics and biologic behavior. MAIN OUTCOME MEASURES: We analyzed various histopathologic parameters and an immunohistochemical profile consisting of pan-cytokeratin (Pan-CK), epithelial membrane antigen (EMA), CD10, smooth-muscle actin (SMA), S-100 protein, p63, calponin, and carcinoembryonic antigen (CEA). RESULTS: The parotid gland (n = 15) and the palate (n = 15) were common sites involved. The cell types encountered were epithelioid, stellate, plasmacytoid, spindle, clear, and mixed with myxoid, hyaline, or myxohyaline stroma. Immunohistochemical analysis revealed vimentin (100%), CK (74%), EMA (27%), CD10 (62%), SMA (35%), S-100 protein (82%), p63 (28%), and calponin (98%) positivity and CEA (100%) negativity. Cervical node dissection was performed in 17 cases: 7 showed nodal metastasis, 2 with pure spindle-cell morphologic characteristics and 3 with spindle cells mixed with other cells. Distant metastasis was noted in 3 of these 7 cases: 2 of these 3 cases showed spindle-cell morphologic characteristics. CONCLUSIONS: Myoepithelial carcinomas showed varied cell types and patterns leading to a wide range of differential diagnoses. Immunohistochemical analysis helped determine the diagnosis. Spindle morphologic characteristics were observed with nodal and distant metastasis.

Small intestinal presentation of nodular lymphocyte-predominant Hodgkin lymphoma with T cell/histiocyte-rich B cell lymphoma-like areas-with review of literature on extranodal presentation of this disease.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), accounts for ∼5% of all cases of Hodgkin lymphoma and is characterized by involvement of the peripheral lymph nodes. NLPHL occurs in young adults and is associated with frequent relapses. In 3% to 7% of cases, NLPHL progresses to a diffuse large B cell lymphoma. Furthermore, a proportion of NLPHL also have areas with features of T cell/histiocyte-rich large B cell lymphoma (THRLBCL), either at presentation or on follow-up. Here, we describe a 32-year-old man who presented to the emergency department with small bowel perforation. The resected small bowel showed full-thickness mural ulceration and involvement by a lymphoma with features of NLPHL that also had areas resembling THRLBCL. The patient had axillary lymphadenopathy, biopsy of which showed NLPHL with focal THRLBCL-like areas. Such a lymphoma presenting as small intestinal lesion/perforation has not been reported in the literature before. We take this opportunity to review the literature on extranodal presentations of NLPHL and discuss the natural history of this disease.

Unusual presentation of primary cardiac lymphoma.

Cardiac lymphomas are rare neoplasms and account for a minor proportion of primary cardiac malignancies. Secondary involvement of the heart and pericardium by systemic lymphoma is well documented, but primary lymphomas of heart and pericardium are extremely rare, accounting for approximately 2% of all primary cardiac tumours. Most cases are diagnosed at autopsy, but nowadays, with modern imaging technologies, early diagnosis and treatment is possible. Here, we present two unique incidental presentations of primary cardiac lymphomas (PCL), one in an atrial myxoma and other involving a valvular homograft and discuss the potential pitfalls and prognosis of this rare entity.

Unusual presentation of metastatic adenocarcinoma.

BACKGROUND: The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy. CASE PRESENTATION: A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 x 2 cm adrenal mass was detected, which increased in size over a period of time to 3 x 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma. CONCLUSION: The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.