Rosai-Dorfman disease of multiple organs, including the epicardium: An unusual case with poor prognosis

Rosai-Dorfman disease (RDD) is a benign proliferative histiocytic disorder predominantly of the lymph nodes with extranodal involvement in some cases. However, serous membranes are seldom involved in the extranodal cases, and epicardial involvement is never reported. Most RDD cases show a self-limiting process with good prognosis and corticosteroid treatment in some patients exhibiting good effect. We recently observed a case of RDD primarily manifesting pericardial and bilateral pleural effusion that finally led to death, and corticosteroid treatment showed little effect. Autopsy showed the characteristic S100-positive and CD68-positive histiocytes exhibiting emperipolesis in the lungs, pleura, epicardium, mediastinal lymph nodes, and colon. This case illustrates the importance of RDD in the differential diagnosis of effusion in multiple serous cavities. The failure of corticosteroid therapy in this patient and her death showed the poor prognosis of some patients with RDD. Moreover, to our knowledge, epicardial involvement of RDD has not been reported.     

Acute Tubulointerstitial Nephritis in Rosai-Dorfman Disease Mimicking IgG4-related Disease

Rosai-Dorfman-Destombes disease (RDD) is a non-Langerhans cell histiocytosis characterized by the accumulation of histiocytes inside the lymph nodes or extranodally. The association between RDD and IgG4-related disease (IgG4-RD) is discussed. We herein report a case of RDD manifesting as acute tubulointerstitial nephritis mimicking IgG4-RD. The first renal biopsy showed severe tubulointerstitial nephritis with infiltration of S100-positive histiocytes and IgG4-positive plasma cells; storiform fibrosis and obliterative phlebitis were not confirmed. After prednisolone therapy, IgG4-positive cells and S100-positive histiocytes were decreased, but the IgG4/IgG ratio increased despite clinical improvement. These findings indicated extranodal RDD in the kidney presenting as tubulointerstitial nephritis.     

Intrahepatic Lymphatics Opacified during Hepatic Arteriography in a Patient with Hepatocellular Carcinoma

Extrahepatic lymph node metastases are not uncommon in advanced cases of hepatocellular carcinoma (HCC). This is the account of a HCC case in which intrahepatic lymphatics running toward the hepatic hilus were clearly opacified during hepatic arteriography. The patient was treated by hepatic artery embolization followed by selective embolization of the portal branches, but lymph node metastases at the hepatic hilus were later found during follow-up. The clinical course of this case suggests that the communication between the tumor and the lymphatics was responsible for the lymph node metastasis.     

Intrahepatic cholangiocarcinoma with micrometastasis in the portal tract of the liver

Intrahepatic metastasis of intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. We report a case of mass-forming type ICC with micrometastasis to the distant portal tract in a 40-year-old woman. In 2006, she was given a diagnosis of mass-forming type ICC, 4 cm in diameter, and right hepatectomy with lymph node dissection was performed. Macroscopic findings showed an irregular white mass-forming type lesion with two small daughter lesions and portal vein invasion in the S5 subsegment. Microscopically, other cancer cells within vessels had proliferated in the peripheral portal tract of the S8 subsegment, and these cancer cells in the portal tract had invaded the vessel wall. The endothelial cells of the vessels around the cancer cells were positive for CD34, but negative for D2-40 and CK19 on immunohistochemical analysis. Therefore, intrahepatic metastasis of cancer cells through the portal vein was diagnosed. Intrahepatic metastasis of cancer cells through the portal vein was demonstrated in a patient with mass-forming ICC.     

CT扫描三维重建技术在巨块型原发性肝癌可切除性评估中的应用

目的探讨计算机断层扫描(CT)三维重建技术在巨块型原发性肝癌(PLC)可切除性评估中的应用价值。方法 2018年1月～2020年1月我院收治的68例巨块型PLC患者,术前行CT检查,应用三维可视化软件-MI-3DVS完成三维重建,观察肿瘤大小、形态、血供及其与周围组织的关系,评判肿瘤的可切除性。以术后组织病理学检查和实际手术为金标准,通过一致性分析CT扫描三维重建评估的效能。结果术前,68例患者均完成CT扫描三维重建,发现肿瘤累及肝动脉18例,肿瘤累及门静脉20例,淋巴结转移12例;经评估,42例(61.8%)巨块型PLC患者可行切除性手术,而在实际手术过程中,45例(66.2%)患者接受了切除性手术治疗;经一致性分析发现,CT扫描三维重建评估肿瘤累及肝动脉的灵敏度为84.2%,特异度为95.9%,准确率为92.6%,阳性预测值为88.9%,阴性预测值为94.0%,Kappa为0.814;肿瘤累及门静脉的灵敏度为86.4%,特异度为97.8%,准确率为94.1%,阳性预测值为95.0%,阴性预测值为93.8%,Kappa为0.862;评估淋巴结转移的的灵敏度为84.6%,特异度为98....     

Metastasis of primary gallbladder carcinoma in lymph node and liver

AIM: To evaluate the patterns with metastasis of gallbladder carcinoma in lymph nodes and liver. METHODS: A total of 45 patients who had radical surgery were selected. The patterns with metastasis of primary gallbladder carcinoma in lymph nodes and liver were examined histopathologically and classified as TNM staging of the American Joint Committee on Cancer. RESULTS: Of the 45 patients, 29 (64.4%) had a lymph node positive disease and 20 (44.4%) had a direct invasion of the liver. The frequency of involvement of lymph nodes was strongly influenced by the depth of the primary tumor (P= 0.0001). The postoperative survival rate of patients with negative lymph node metastasis was significantly higher than that of patients with positive lymph node metastasis (P= 0.004), but the postoperative survival rate of patients with Nl lymph node metastasis was not significantly different from that of patients with N2 lymph node metastasis (P= 0.3874). The postoperative survival rate of patients without hepatic invasion was significantly better than that of patients with hepatic invasion (P= 0.0177). CONCLUSION: Complete resection of the regional lymph nodes is important in advanced primary gallbladder carcinoma (PGC). The initial sites of liver spread are located mostly in segments IV and V. It is necessary to achieve negative surgical margins 2 cm from the tumor. In patients with hepatic hilum invasion, extended right hepatectomy with or without bile duct resection or portal vein resection is necessary for curative resection.     

Two cases of gastrointestinal stromal tumor of the stomach with lymph node metastasis

Lymph node metastasis from gastrointestinal stromal tumor (GIST) is quite rare. We report two cases of gastric GIST with nodal metastases and results of their mutation analyses. In the first case (78-year-old male), a mass 4.0 cm in size was located at the gastric cardia. Proximal gastrectomy was performed. In the other case (40-year-old female), the gastric tumor was 2.5 cm in size. Computed tomography scan revealed a hepatic metastasis. Imatinib mesylate was administered as primary treatment, at the patient's preference, but the tumors exhibited no response. Wedge resection of the stomach and partial hepatectomy were performed. In both cases, histological examination revealed that the tumors consisted of spindle cells. In the former case, there was an isolated lymph node metastasis at the right cardia. In the latter, three of 5 sampled nodes adjacent to the tumor were positive. In both cases, immunohistochemical analyses showed that primary and metastatic tumors were diffusely positive for CD117 and CD34 and negative for desmin and S100-protein. In the former case, there was a deletion mutation in CD117 exon 11, the most common genotype in GIST. In the latter, there were no detectable mutations in CD117 or platelet-derived growth factor receptor alpha.     

Long-term survival of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement

We report the case of a very rare 6-year disease-free survivor of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement. A 76-year-old female with liver dysfunction was referred to our institution. Contrast-enhanced computed tomography showed a 5-cm low-density tumor with irregular marginal enhancement in the left and caudate lobes of the liver. Cholangiography revealed complete obstruction of the left hepatic bile duct. Angiography showed obstruction of the left branch of the portal vein. Metastasis to the hilar lymph nodes was disclosed at surgery. The patient underwent left hepatectomy with caudate lobectomy, resection of the extrahepatic bile duct, and lymphadenectomy. The total vascular exclusion of the liver was used for hepatectomy and reconstruction of the portal vein. Microscopically, the tumor was a poorly differentiated adenocarcinoma with many infiltrating lymphocytes, and extensive necrosis was present within the tumor. The experience gained in the present case suggests that aggressive surgery may be a potential approach to provide a hope of long-term survival for patients with intrahepatic cholangiocarcinoma despite the presence of regional lymph node metastasis and vascular invasion.     

Rosai-Dorfman Disease of the Central Nervous System: Report of 6 Cases and Review of the Literature

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement.     

Thyroid involvement in Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD) with thyroid involvement is extremely rare; we herein present the sixth known case with a review of the previously reported five cases and discuss the clinicopathological characteristics of this entity. RDD with thyroid involvement has occurred only in females with a mean age of 56.3 years, which is significantly different from nodal RDD predominantly seen in young males. Besides this, autoimmune thyroiditis is frequently associated in RDD with thyroid involvement, which raises a suspicion of a common pathogenesis of both entities. RDD with thyroid involvement is commonly misdiagnosed preoperatively as thyroid malignancy with lymph node metastasis, which may lead to overtreatment and postoperative complication. Clinical presentations might be helpful for a preoperative differential diagnosis; while thyroid function, sonography, thyroid isotope scan, and fine needle aspiration have been less useful. All six cases were treated by surgery and complete remission was seen. However, two patients with a preoperative diagnosis of benign disease suffered from hypothyroidism due to total thyroidectomy.     

Cyclin D1 expression and novel mutational findings in Rosai-Dorfman disease

Rosai-Dorfman disease (RDD) is an enigmatic histiocytic disorder classically diagnosed by a distinctive combination of pathological features: emperipolesis, or migration of intact haematological cells through the voluminous cytoplasm of lesional histiocytes, and expression of S100 by these histiocytes. The pathogenesis has long been elusive until the recent detection of recurrent and mutually exclusive mutations in several oncogenes in the mitogen-activated protein kinase (MAPK) pathway. Based on these findings, we investigated a cohort of 21 RDD patients and found that the lesional histiocytes in 86% (18/21) of patients exhibited strong and diffuse nuclear Cyclin D1 expression, which not only may provide a diagnostic marker for this sometimes pathologically challenging disease, but also probably reflects constitutive MAPK pathway activation because we additionally identified phosphorylated-ERK expression in 90% (19/21) of cases. Further, we performed massively parallel sequencing on a subset (6/18) of the CyclinD1 positive cases, identifying several mutations that have not been previously reported in RDD. Taken together, our findings bolster the concept of RDD as a disease of MAPK activation in a substantial percentage of cases and enhance the current understanding of the pathogenesis of RDD.     

Erdheim chester - A rare disease with unique endoscopic features

Erdheim-Chester disease (ECD) is a rare inflammatory syndrome in which systemic infiltration of non-Langerhans cell histiocytes occurs in different sites. Both the etiology and pathophysiology of ECD are unknown, but CD68 positive CD 1a/S100 negative cells are characteristic. The presentation of ECD differs according to the involved organs. This case report describes a patient with ECD and the gastrointestinal manifestations and unique endoscopic appearance as seen in gastroscopy and colonoscopy with histological proof of histiocyte infiltration of the lamina propria. The clinical and endoscopic findings of this unique case, to our knowledge, were never described before, so were the features of the gastrointestinal involvement in this disease.     

ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy

We report 3 cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia, and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK(+) histiocytosis. The disease in the 3 patients (2 having been given chemotherapy) resolved slowly over many months.     

Cholangiocarcinoma coincident with schistosomiasis japonica

The relationship of parasitic liver disease to cholangiocarcinoma has long been debated, and it has been reported that cholangiocarcinoma is associated with opisthorchiasis viverrini. We report herein a rare case of cholangiocarcinoma associated with schistosomiasis japonica. A 76-year-old Japanese man with jaundice was diagnosed with cholangiocarcinoma. Radical resection was not done because of hepatic arterial and portal vein invasion. Biliary microwave tissue coagulation therapy was performed with placement of a metallic stent endoprosthesis. Twenty-two months after the treatment, however, the patient died from hematemesis. Autopsy findings revealed that there was no distant metastasis, even in the area of regional lymph node metastasis. The primary tumor in the hepatic hilar region had been replaced by necrotic debris resulting from the microwave therapy, and an expandable metallic stent was located in the center of the debris. Histological findings showed schistosome eggs, which were old and microcalcified, in veins in the colonic submucosa. Glissons fibrosis around the cancer lesion suggested that schistosomiasis japonica and cholangiocarcinoma can occur together with severe chronic inflammation of the portal vein.     

An esophageal gastrointestinal stromal tumor with regional lymph node metastasis

We report a case of a 72-year-old woman with an esophageal gastrointestinal stromal tumor (GIST) with regional lymph node metastasis. Endoscopy and barium esophagography revealed a large submucosal tumor in the lower esophagus. Computed tomography showed a solid 8-cm tumor, suggesting an esophageal mesenchymal tumor. Endoscopic ultrasonography-guided fine-needle aspiration biopsy was positive for c-KIT and CD34, and negative for desmin and S-100. The patient underwent middle and lower esophagectomy via left thoracotomy, followed by gastric tube reconstruction. The tumor was completely resected, but a metastasis in the right paracardial lymph node was observed. Pathological examination confirmed the tumor to be high risk. We are carefully following up the patient.     

A case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease

We report a case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease. A 48-year-old woman with von Recklinghausen disease was referred to our hospital because of a submucosal tumor at the ampulla of Vater detected by upper gastrointestinal endoscopy. The lesion was diagnosed as a carcinoid tumor based on the pathology of the biopsy specimen. At operation, although there were liver metastasis on the surface of S3 the liver and regional lymph node metastases, we selected pancreatoduodenectomy with lymph node dissection and enucleation of the liver metastasis. The postoperative course was good and the woman was discharged on postoperative day 33. No recurrence has been seen at 24 months since surgery.     

Rosai–Dorfman disease with factor XII deficiency

A 17-year-old female patient presented with chronic symmetrical oligoarthritis of both knees and ankles, xerostomia, xerophthalmia, multiple bilateral lymphadenopathies in the cervical region, and bilateral parotid enlargement with the histological finding of chronic sialoadenitis. She had been already given methotrexate, chloroquine, and corticosteroids with the diagnosis of rheumatoid arthritis (RA) before referral to our outpatient clinic. Because her complaints and the lumps did not remit and she could be classified as neither RA nor primary Sjögren’s syndrome (SS) according to 1987 ACR RA criteria or European preliminary criteria for SS, lymph node biopsy was repeated and revealed the diagnosis of Rosai–Dorfman disease (RDD) with the histological findings of histiocytes, phagocyting lymphocytes in enlarged sinuses, and mature plasma cells infiltrating the pulpa. All the medications were stopped after the pathological diagnosis of RDD and consulting with the Division of Hematology. She was reevaluated with magnetic resonance imaging, which showed dense infiltrative areas around knee and ankle joints, and computed tomography that showed a soft tissue mass surrounding the descending aorta and upper part of the abdominal aorta. Activated partial thromboplastin time was found to be prolonged in prebiopsy examinations, and factor XII deficiency was detected after detailed hematological evaluation. The symptoms of joint involvement were relieved with nonsteroidal antiinflammatory drugs. She has been followed-up without medication without obvious clinical or laboratory change. We herein report a patient with RDD mimicking RA and SS. We consider that RDD should be kept in mind especially in patients with resistant symptoms to conventional therapies, younger disease onset, and predominant parotid and lymph node enlargement.     

Preliminary results with "ex situ" surgery for hepatic tumors: an alternative between palliative treatment and liver transplantation?]

We report 3 cases of liver tumors which were unsuitable for conventional resection and which were removed using a technique combining hypothermic portal perfusion with an anhepatic period of more than 2 hours. The liver was mobilized after section of the infra- and supra-hepatic inferior vena cava in 2 cases. The tumor was a cholangiocarcinoma in 2 cases and colonic metastasis in 1 case. Non-tumoral liver parenchyma was normal in all cases. The inferior vena cava was involved by the tumor in 2 cases. Complete tumor resection was achieved in all cases, but required reconstruction of the hepatic veins in 1 case. Two patients in whom portal venous bypass was not used developed hemodynamic failure after liver revascularization. One of them died. In patients without underlying chronic liver disease and with unresectable tumor by conventional technique, "ex situ" resection can be a worthwhile therapeutic alternative.     

Malignant nerve sheath tumor of the esophagus (malignant esophageal schwannoma)

A case of malignant esophageal schwannoma is reported. A 54-year-old man consulted for a 1-year history of dysphagia. Investigations revealed a tumor of the distal esophagus, with involvement of the cardia, and were suspicious for metastatic mediastinal nodes. Ivor-Lewis esophagectomy with gastric-tube reconstruction was performed, with favorable outcome. Histological examination revealed esophageal sarcoma in a Barrett's esophagus. Periesophageal nodes had metastatic involvement. Immunohistochemical study was positive for S100 and vimentin and was negative for CD117, compatible with a diagnosis of esophageal schwannoma. We discuss this rare disease and its characteristics. This is the second reported case of malignant schwannoma with lymph node metastasis.