Giant cell granulamatous hypophysitis with remarkable uptake on Gallium-67 scintigraphy

We treated a man with giant cell granulomatous hypophysitis with pituitary enlargement, as seen on magnetic resonance imaging. Endocrinological examination revealed panhypopituitarism and diabetes insipidus. Microscopic examination of the specimen obtained by transsphenoidal pituitary biopsy revealed a granulomatous lesion, composed of epitheliod cells, Langhans' multinucleated giant cells, lymphocytes and other chronic inflammatory cells. On whole body gallium-67 scintigraphy, there was extensive uptake in the pituitary gland. Gallium-67 scintigraphy may greatly aid in the diagnosis of granulomatous hypophysitis.     

Granulomatous hypophysitis with meningitis and hypopituitarism.

We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis.     

High mast cell density associated with granulomatous formation in tuberculous lymphadenitis

Mast cells are one of the main inflammatory cells involved in the pathogenesis of tuberculosis. Previous reports revealed that mast cells participated in both acute and chronic states of infection with Mycobacterium tuberculosis through direct contact or indirect enhancement by releasing mediators. The authors evaluated mast cell density on tissue sections of tuberculous lymphadenitis stained with 0.1% toluidine blue from 45 cases, all of which were retrieved from the surgical pathology files of King Chulalongkorn Memorial Hospital from 1999 to 2006. A number of mast cells were correlated semiquantitatively with granulomas which were formed by aggregation of epithelioid histiocytes, multinucleated giant cells, and caseous necrosis. We found that mast cell density was significantly increased in lymph nodes with greater granuloma involvement (p = 0.030) and multinucleated giant cell formation (p = 0.010). These findings indicate a significant correlation between mast cell density and the granulomatous formation responsible for M. tuberculosis.     

Combined hepatocellular carcinoma and neuroendocrine carcinoma with sarcomatous change of the liver after transarterial chemoembolization

Primary hepatic neuroendocrine carcinoma is rare and its origin is not clearly understood. An admixture of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is particularly rare. Here, we report a patient with an extremely rare combination of HCC and neuroendocrine carcinoma of the liver. To our knowledge, this is the first reported case in which the carcinoma showed sarcomatous change. The patient was a 76‐year‐old man who had received outpatient treatment for chronic hepatitis C. On abdominal computed tomography (CT), the hepatic tumor was enhanced in the arterial phase but its density was lower than that of normal liver in the portal phases. His serum α‐fetoprotein (AFP) level was very high. Therefore, transarterial chemoembolization (TACE) was performed based on the diagnosis of HCC. Ten months after TACE, his serum AFP level had increased to the level measured before TACE. Partial hepatectomy was performed because CT revealed poor enhancement of the recurrent tumor. Histopathologically, the tumor consisted of two distinct components: moderately differentiated HCC was intermingled with a neuroendocrine carcinoma, which was accompanied by sarcomatous changes. Immunohistochemically, the neuroendocrine carcinoma cells were positive for CD56, chromogranin A and neuron‐specific enolase, and negative for AFP. The sarcomatous area was positive for AE1/3 and CD56, consistent with sarcomatous change of neuroendocrine carcinoma. The neuroendocrine carcinoma and/or sarcomatous change may have been due to phenotypic changes and/or dedifferentiation of HCC induced by TACE. Six months after surgery, the patient was diagnosed with metastasis of the neuroendocrine carcinoma to sacral bone. He died 7 months after surgery.     

An autopsy case of sudden death in a patient with giant cell myocarditis

We present a case of a 28-year-old male weight lifter who died suddenly while driving a bicycle. Forensic autopsy and histopathological examinations revealed granulomatous lesions in the myocardium and hilar lymph nodes. The latter had massive caseation necrosis, epithelioid granulomas and Langhans' giant cells suggestive of tuberculosis. However, the myocardium showed predominantly multinucleated foreign body and myogenic giant cells, lymphocytes, plasma cells, macrophages, eosinophils. Staining for acid-fast bacilli was negative. The present case highlights the difficulty in establishing whether the granulomatous lesions in the hilar lymph nodes and the myocardium are incidental findings or whether they are related by the same pathogenetic mechanisms.     

A case of spontaneous femoral neck fracture associated with multicentric reticulohistiocytosis. Oversecretion of interleukin-1β, interleukin-6, and tumor necrosis factor α by affected synovial cells

We describe a case of left femoral neck fracture associated with multicentric reticulohistiocytosis (MR). Biopsy specimens from a skin nodule and from synovial tissue showed histiocytic multinucleated giant cells (MR cells) that are characteristic of MR. A surgical specimen from the resected femoral head revealed that multinucleated giant cells and mononuclear cells invaded the marginal subchondral bone, without evident pannus. These cells also infiltrated into the fracture site, with bone resorption by activated osteoclasts. Immunohistochemical studies of synovium from the left hip joint showed positive staining for interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α, and abundant cytokine production by cultured synovial cells was demonstrated. These findings suggest that the subchondral invasion and intramedullary infiltration by MR cells caused articular destruction and/or fracture as a result of oversecretion of the cytokines.     

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients tha     

Risk factors for the leakage of chemotherapeutic agents into systemic circulation after transcatheter arterial chemoembolization of hepatocellular carcinoma

This prospective study was to investigate the possible risk factors for the leakage of chemotherapeutic agent into the systemic circulation after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Peripheral plasma concentrations of chemotherapeutic agents were determined at 1 hour and 72 hours after TACE by high-performance liquid chromatography in 53 patients. HCC were divided into three types namely single nodule (<5 cm), multiple nodules (all <5 cm), and main nodule measuring 5 cm or more. Forty-four patients (83%) showed detectable chemotherapeutic concentrations within 72 hours after TACE. Patients with single nodular-type HCC had lower incidence of detectable plasma chemotherapeutic agents after TACE than the other two groups (all p < 0.05). The injected doses of lipiodol, epirubicin, and mitomycin C were lower in patients without detection than in patients with detectable chemotherapeutic agents (all p < 0.05). Multivariate logistic regression showed that tumor type and injected dose of lipiodol were two independent risk factors for the leakage of mitomycin C at 1 hour after TACE (all p < 0.05), and the injected dose of mitomycin C was the risk factor for the leakage of epirubicin at 1 hour after TACE (p < 0.05). In conclusion, multiple nodular type and large nodule measuring 5 cm or more have a risk of leakage of mitomycin C after TACE. Injected dose of lipiodol and mitomycin C as risk factor for the leakage of mitomycin C and epirubicin respectively may be because of competition of their injected volume within the limited space of target.     

Idiopathic giant-cell granulomatous hypophysitis mimicking acute meningitis.

A 32-year-old woman presented with severe headache, photophobia, fever, nausea, vomiting, and worsening vision. She had also noted several months of amenorrhea. She was febrile to 38.9 degrees C. Laboratory evaluation revealed a markedly elevated erythrocyte sedimentation rate. Lumbar puncture revealed a cerebrospinal fluid lymphocytic pleocytosis and an elevated protein level. Endocrine studies revealed evidence of panhypopituitarism without diabetes insipidus. A magnetic resonance imaging study showed a 2-cm pituitary mass with optic chiasmal compression. The patient had a trans-sphenoidal resection of the mass. Pathology revealed multinucleated giant cells in necrotic debris, but no evidence of pituitary tumor. Studies looking for evidence of systemic granulomatous disease were negative. The patient was considered to have idiopathic giant-cell granulomatous hypophysitis. After surgery, the patient's vision improved and hormone replacement therapy was initiated. This case illustrates that idiopathic giant-cell granulomatous hypophysitis should be considered in the differential diagnosis of a patient presenting with a pituitary mass, hypopituitarism, and meningitis-like symptoms.     

Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization

Background and Aim: Transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for non‐curative hepatocellular carcinoma (HCC), and hoped to have chemotherapeutic and ischemic effects; however, the histopathological changes of HCC caused by TACE have not been sufficiently discussed so far. We aimed to assess the morphological and immunohistochemical features of HCC treated with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to correlate these data with observed clinicopathological characteristics. Methods: Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of HCC resected without TACE as a control were analyzed. Results: The incidences of intrahepatic metastasis, poorly differentiated histology, multinucleated giant cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were significantly higher than those in the non‐TACE group. The TACE group showed reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in 23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the TACE group was significantly higher than in the non‐TACE group (P = 0.0423). There was no correlation between immunoreactivity and the number of times TACE was carried out, but the expression of CK19 and vimentin in the massive necrotic group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229, respectively). Only TACE was an independent determinant of CK19 expression in all cases by multivariate analysis. Conclusions: These results suggest that preoperative TACE may have an impact on the biliary phenotype of HCC. Some post‐therapeutic HCC patients might develop HCC with a biliary phenotype indicating more aggressive malignancies.     

Direct invasion to the colon by hepatocellular carcinoma： Report of two cases

Although hepatocellular carcinoma （HCC） is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization （TACE） for HCC 1.5 years prior to admission to our hospital. Computed tomography （CT） showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.     

Granulomatous slack skin or granulomatous mycosis fungoides – a case report.

A 46-year-old man presented with circumscribed inflammatory poikilodermatic lesions of loose skin on the upper arm. Histologic examination disclosed a heavy lymphocytic infiltrate of the whole dermis and the upper part of the subcutaneous fat tissue with a predominant T-helper phenotype and about 10% of Mac 387-positive macrophages and some scattered multinucleated giant cells. Lymphocytic cells were aligned along the epidermal basement membrane and showed focal epidermotropism. In part these cells had multilobular nuclei. The diagnosis of granulomatous mycosis fungoides versus early granulomatous slack skin was made. The patient was treated with a combination of radiotherapy (total dose 36 Gy) and interferon-alpha as a maintenance treatment which resulted in complete remission and disease-free survival of 27 months up to now.     

Microscopic colitis with granuloma which responded to steroid therapy

We present a patient with chronic watery diarrhea and weight loss, in whom colonoscopic findings were consistent with microscopic colitis, but histopathological examination revealed granulomatous inflammation. A 67-year-old Japanese female with a several year history of chronic watery diarrhea and body weight loss was admitted to our hospital. Her laboratory data showed hypoalbuminemia and high levels of serum immunoglobulin G and C-reactive protein. Colonoscopic findings were grossly normal. Histopathology showed inflammatory cell infiltrates with non-necrotizing granulomas and multinucleated giant cells, indicating that this was not conventional microscopic colitis, lymphocytic colitis or collagenous colitis. After treatment with prednisolone her symptoms and laboratory data improved dramatically, and she went into remission without the necessity of further steroid treatment.     

A case of multiple myeloma presenting as giant chest wall tumors with calcification]

A 60-year-old man was admitted for investigation of an abnormality detected in chest radiography: a giant tumor with calcification in the right middle lung field. A computed tomography (CT) scan revealed multiple tumors with calcification on the posterior chest wall. Histological analysis of the tumor specimen obtained by surgical biopsy demonstrated an increasing number of plasma cells accompanied with the deposition of amyloid. A bone marrow biopsy contained over 50% of plasma cells. We therefore diagnosed these tumors as multiple myeloma. It has been reported that multiple myeloma is usually characterized by osteolytic lesions; osteosclerotic changes are rare. Multiple myeloma should be taken into account as one of the causes of a chest wall tumor even if it is diffusely calcified.     

A case of malignant tumor of the ascending part of duodenum with osteoclast-like giant cells

Extraskeletal neoplasms with osteoclast-like giant cells are very rare. These tumors are most frequently reported in the breast and pancreas, and but rarely in other sites. We report a case of duodenal malignant tumor with osteoclast-like giant cells. The patient was a 76-year-old man who presented with vomiting. Computed tomography, magnetic resonance imaging, and gastrointestinal endoscopy revealed a giant tumor in the ascending part of duodenum. Biopsy specimens showed an undifferentiated malignant tumor with benign multinucleated giant cells. Immunohistochemical staining indicated that the tumor cells were reactive with vimentin, but not with epithelial markers or the other mesenchymal markers, and the multinucleated giant cells were reactive with CD68. Thus, we diagnosed a malignant tumor of the ascending part of duodenum with osteoclast-like giant cells. To the best of our knowledge, this is the first case of duodenal malignant tumor with osteoclast-like giant cells in Japan.     

Characteristics of giant cells and factors related to the formation of giant cells in myocarditis

Giant cell myocarditis is a serious and frequently fatal inflammatory heart disease of which the etiology remains unknown. In the present study, we investigated the origin of multinucleated giant cells in myocarditis with the use of an experimental model. We also examined the factors relating to the formation of giant cells in myocarditis. Severe myocarditis characterized by the appearance of multinucleated giant cells was induced in Lewis rats by immunization with cardiac myosin in complete Freund's adjuvant. Two types of giant cells, foreign body giant cell-like and myocytelike, were observed in this myocarditis. Immunohistochemical studies revealed that both types of multinucleated giant cells were stained with OX42 and ED1 (macrophage markers) and were not stained with anti-desmin antibody and HHF35 (markers for muscle fibers). Therefore, it is likely that multinucleated giant cells in this myocarditis are derived from macrophages. During the course of the disease, the appearance of multinucleated giant cells was restricted to a period corresponding with the fulminant phase of inflammation. When the severity of the disease was modulated by immunization with various doses of the antigen, multinucleated giant cells appeared only in severe myocarditis after inoculation of a large dose of the antigen. Administration of immunoadjuvants also affected the formation of giant cells. Most of the rats injected with cardiac myosin in complete Freund's adjuvant developed giant cell myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)     

CT volume measurement for prognostic evaluation of unresectable hepatocellular carcinoma after TACE

AIM:To analyze the value of computed tomography(CT) volume measurements for evaluation of the survival rate of unresectable hepatocellular carcinoma(HCC) patients after transcatheter arterial chemoembolization(TACE).METHODS:One hundred and sixty-six unresectable HCC patients after TACE were involved in this retrospective study.Hepatic CT scan was performed for all patients before and 4 wk to 2 mo after TACE to def ine the morphologic features of HCC including its largest diameter,volume,product of the great...     

肝动脉化疗栓塞术治疗中晚期原发性肝癌的疗效观察

[目的]研究经导管肝动脉化疗栓塞术(TACE)治疗中晚期原发性肝癌的疗效并预测影响患者生存率的相关因素。[方法]80例中晚期原发性肝癌患者经1次或多次TACE治疗后,分别于治疗后第1、3、6、12个月对患者进行CT扫描评估肿瘤对治疗的反应并计算生存率。[结果]对所有患者随访观察3年(或者观察至死亡),80例患者共进行了163次TACE,按Child-pugh分级A级48例(60.0%),B级32例(40.0%);肿瘤大小5cm 18例(22.5%),5~10cm 42例(52.5%),10cm 20例(25.0%);行1、2、3、4次TACE的患者分别为12、56、9、3例;1、2、3年的总生存率分别为71.3%、43.8%和17.5%,肿瘤直径5cm患者TACE后3年生存率显著高于肿瘤直径为5~≥10cm患者。[结论]TACE是治疗中晚期肝癌的一种有效的方法,能有效缓解患者的临床症状并延长生存期,初始肿瘤的大小是决定患者生存率的独立影响因素。     

Renal involvement in Crohn's disease: granulomatous inflammation in the form of mass lesion

Extraintestinal manifestations of Crohn's disease (CD) are varied and concentrated mainly to the skin and eye. Urinary tract or renal involvement is extremely rare. Herein we report on a case of renal lesion of a 50-year-old woman with a 15-year history of CD. Abdominal computed tomography scan of the patient identified heterogeneous multinodular mass lesions in the left kidney. Histology proved classic granulomatous inflammatory nodules with multinucleated giant cells, eosinophils, plasma cells, epithelioid cells, and spindle-shaped myofibroblasts in the areas, where the computed tomography scan indicated. After the extensive PubMed search in the literature, this is the first macroscopically documented and histologically proved, mass-like renal involvement in CD. From now on, differential diagnostics of renal mass lesions in CD should include the tumor-like, Crohn's-type granulomatous inflammation as direct kidney manifestation of the disease.     

Cardiac sarcoidosis

The present report describes a patient with cardiac sarcoidosis who developed complete right bundle branch block, complete atrioventricular block and subsequent congestive heart failure. The patient demonstrated no clinical evidence of systemic sarcoidosis. Upon postmortem examination, the myocardium showed extensive noncaseating granuloma with numerous multinucleated giant cells. An initial routine microscopic examination of the lung revealed no evidence of granulomatous lesions. However, an extensive microscopic examination of the lung using serial sections demonstrated inconspicuous granulomatous lesions with giant cells. Thereby, a diagnosis of sarcoidosis was made. All other organs were free of granulomatous inflammation in spite of an extensive microscopic examination through serial sections. The present case suggests that a careful and extensive microscopic examination of the other organs may be necessary to establish a diagnosis of cardiac sarcoidosis.