A rare case of Ewing sarcoma with elevated plasma pro-gastrin-releasing peptide (proGRP) level

We studied a 17-year-old Japanese male with huge mass arising from the left third rib. The mass compressed the left lung and adhered to the pericardium, but the patient had no distant metastasis. He had a high level of plasma pro-gastrin-releasing peptide (proGRP). Histopathological examination of the bone biopsy specimen revealed small round cell tumor which was immunohistochemically positive for CD99 and vimentin. Gene analyses demonstrated EWSR1-FLI1 fusion, confirming the pathological diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). Several cycles of chemotherapy resulted in clinical good partial response, and plasma proGRP level at that time was normalized. Thereafter residual tumor was resected. Histopathological examination of the resected specimen showed no viable tumor cells, verifying the pathological complete response. High level of plasma proGRP before the chemotherapy and its normalization after the successful chemotherapy strongly suggest that ES/PNET in the present case was a proGRP producing tumor

A case of Carney complex misdiagnosed as neurofibromatosis type 1 – Diagnostic difficulty in a rare disease

We experienced a diagnostically challenging case of Carney complex (CNC). A 24-year-old woman had a past history of surgical removal of multiple cutaneous tumors in the childhood. She was followed as a patient of neurofibromatosis type 1 (NF1) and referred to our hospital for further treatment after she grew up to adulthood. At our hospital, several cutaneous tumors were excised, and the pathological diagnosis was myxoma arising from not deep soft tissue but cutis (so-called cutaneous myxoma). Despite previous clinical diagnosis of NF1, because of the probability of CNC, detailed systemic examination was undertaken including radiological and endocrinological tests. Imaging techniques showed multiple lumps in both breasts, a mass in left atrium and nodular lesions in adrenal glands. Serum ACTH level was markedly suppressed. Surgically resected specimens revealed breast myxomas, cardiac myxoma and primary pigmented nodular adrenocortical disease (PPNAD). These findings met the diagnostic criteria for CNC. Genetic analysis revealed known non-sense mutation of PRKAR1A c.124C>T (p.R42X) (ClinVar ID 41382). Her 50-year-old mother was also shown to have cardiac myxomas, radiological finding of breast myxomatosis and the same PRKAR1A mutation as her daughter. In the present case, the accurate diagnosis of CNC was difficult not only because CNC is a rare disease but also because skin pigmentation was not obvious. Since cardiac myxoma might result in poor or fatal outcome, early and accurate diagnosis of CNC and subsequent systemic investigation including heart are important. Although pediatric cutaneous myxomas are rare, multiple cutaneous myxomas might suggest the possibility of CNC. In such cases, systemic investigation should be done for the accurate diagnosis. Keywords: Carney complex, Cutaneous myxoma, PPNAD, PRKAR1A mutatio

Gastric CLTC-ALK fusion-positive inflammatory myofibroblastic tumor showing an endoscopic superficial depressed-type appearance

We present a 76-year-old Japanese male who had a history of removal of a gastric gastrointestinal stromal tumor (GIST) 6 years ago. Although asymptomatic and having no evidence of recurrence, follow-up endoscopy revealed a small, white depressed lesion of approximately 1 cm with converging mucosal folds in the greater curvature of the fundus, which was suspicious of depressed-type early gastric cancer (GC) by conventional endoscopy. However, no evidence of GC except a “white globe appearance”-like area was identified by magnifying endoscopy with blue laser imaging. The biopsy specimens showed a proliferation of anaplastic lymphoma kinase (ALK)-positive spindle cells in the gastric mucosa, and ALK-rearrangement was detected by fluorescent in situ hybridization. Furthermore, clathrin heavy chain (CLTC)-ALK fusion was seen by genetic analysis, thus the lesion was preoperatively diagnosed as gastric inflammatory myofibroblastic tumor (IMT). For the curative intent, a laparoscopic endoscopic cooperative surgery (LECS) was performed. On the specimens resected by LECS, ALK-positive cells were sporadically distributed in the gastric mucosa and submucosa in the depressed area. In addition, two sporadic GISTs originating from the muscularis propria were found under the gastric IMT. Although there have been many reported cases of gastric IMTs, almost all those cases showed huge elevated tumors. Thus, this lesion is an extremely rare IMT case presenting a superficial depressed-type appearance, like 0-IIc type early GC. Keywords: Stomach, Superficial depressed-type, IMT, CLTC-ALK fusio

A case of meningeal myxoid solitary fibrous tumor/hemangiopericytoma with unique NAB2-STAT6 fusion gene and symptomatic intratumoral hemorrhage

We experienced a case of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) with symptomatic intratumoral hemorrhage in a 67-year-old Japanese woman. Her chief complaints were sudden onset of motor aphasia and right hemiparesis. Brain computed tomography showed the hemorrhagic mass adjacent to the superior sagittal sinus. The mass was resected and pathological examination of the specimen revealed a tumor that is rich in vessels and accompanied with intratumoral hemorrhage. Short spindle tumor cells were proliferating with myxoid stroma. Tumor cells appeared to be arranged around the vessels and sometimes attached to the vessel wall directly. Although hyalinization of the vessel wall was observed, neither patternless pattern nor staghorn vessels were seen. Immunohistochemistry revealed that the tumor cells were positive for both CD34 and nuclear STAT6. Moreover, gene analyses revealed unique NAB2-STAT6 fusion. Immunohistochemical findings and fusion-gene analyses enabled us to make the definite diagnosis of meningeal myxoid SFT/HPC. The present case showed the three unique features such as clinically symptomatic intratumoral hemorrhage at the onset, rare variant of myxoid SFT/HPC, and unique NAB2-STAT6 fusion. Keyword: Meninx, Myxoid solitary fibrous tumor/hemangiopericytoma, Cerebral hemorrhage, NAB2-STAT6 fusio

Prognostic role of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography with an image-based harmonization technique: A multicenter retrospective studyCentral MessagePerspective

Objectives: Despite the prognostic impacts of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examination, fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography–based prognosis prediction has not been used clinically because of the disparity in data between institutions. By applying an image-based harmonized approach, we evaluated the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters in clinical stage I non–small cell lung cancer. Methods: We retrospectively examined 495 patients with clinical stage I non–small cell lung cancer who underwent fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examinations before pulmonary resection between 2013 and 2014 at 4 institutions. Three different harmonization techniques were applied, and an image-based harmonization, which showed the best-fit results, was used in the further analyses to evaluate the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Results: Cutoff values of image-based harmonized fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters, maximum standardized uptake, metabolic tumor volume, and total lesion glycolysis were determined using receiver operating characteristic curves that distinguish pathologic high invasiveness of tumors. Among these parameters, only the maximum standardized uptake was an independent prognostic factor in recurrence-free and overall survivals in univariate and multivariate analyses. High image-based maximum standardized uptake value was associated with squamous histology or lung adenocarcinomas with higher pathologic grades. In subgroup analyses defined by ground-glass opacity status and histology or by clinical stages, the prognostic impact of image-based maximum standardized uptake value was always the highest compared with other fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Conclusions: The image-based fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography harmonization was the best fit, and the image-based maximum standardized uptake was the most important prognostic marker in all patients and in subgroups defined by ground-glass opacity status and histology in surgically resected clinical stage I non–small cell lung cancers

An autopsy case of amyloid β-related angiitis with cognitive impairment, multiple infarcts and subcortical hemorrhage

A 76-year-old female presented with cognitive impairment and multiple brain infarcts and died of massive subcortical cerebral hemorrhage. A premortem clinical diagnosis was not possible. She did not show apparent microbleeds on brain images during her lifetime. An autopsy revealed vasculitis at various stages with amyloid β deposition and granulomatous reaction in cortical and leptomeningeal arteries, although almost vasculitic processes were in the healing stage, suggestive of the inactive stage of the disease process. Affected vessels were strictly limited to the brain. The final pathological diagnosis of the autopsy was amyloid β-related angiitis. Genotype analyses of ApoE revealed ApoE ε3/ε3 genotype, low risk for Alzheimer's disease. On retrospective examination, the titer of anti-amyloid β autoantibody in cerebrospinal fluid was rather high in our case, but the exact clinical significance remains unknown. Since microbleeds on brain images are diagnostic findings in patients with cerebral amyloid angiopathy-associated conditions, it is very difficult to make an accurate diagnosis of amyloid β-related angiitis without typical microbleeds or open brain biopsy like our case. Keywords: Amyloid β-related angiitis, Cerebral amyloid angiopathy, ApoE, Subcortical cerebral hemorrhage, Primary central nervous system vasculiti