Naoe Kinoshita

Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes

CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.

Mucosa-associated lymphoid tissue lymphoma of the thymus associated with Sjögren’s syndrome: Report of a case

A 68-year-old Japanese man with Sjögren’s syndrome was pointed out to have a nodular shadow in the anterior mediastinum. The tumor was resected under video-assisted thoracoscopy and it was pathologically diagnosed to be thymic mucosa-associated lymphoid tissue (MALT) lymphoma. There has been no recurrence for 17 months after surgery. Mucosa-associated lymphoid tissue lymphoma of the thymus is rare, and its pathological diagnosis requires sufficient knowledge and experience. Since thymic MALT lymphoma is distinct from MALT lymphoma of other sites in several ways, including gene abnormalities and geographic distribution, an alternative oncogenic pathway and the influence of racial and/or environmental factors must be considered to be involved. However, since the number of reported thymic MALT lymphomas is limited, these issues are still unclear. The accumulation of further similar cases will help to elucidate various issues concerning thymic MALT lymphoma associated with Sjögren’s syndrome.

Sox9 expression in carcinogenesis and its clinical significance in intrahepatic cholangiocarcinoma

BACKGROUND Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. AIMS To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. METHODS Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. RESULTS Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines. CONCLUSIONS Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition.

Adenosquamous carcinoma arising in a thyroglossal duct cyst: Report of a case

A 61-year-old Japanese woman had an 11-year history of an enlarging anterior neck mass that was diagnosed otolaryngologically as a thyroglossal duct cyst. Preoperatively, fine-needle aspiration cytology suggested a neoplastic lesion, but no obvious malignancy was clinically evident. Sistrunk’s operation was performed. An adenosquamous carcinoma arising in a thyroglossal duct cyst was found on pathological examination. Carcinoma arising in a thyroglossal duct cyst is rare, and only approximately 200 cases have been reported, most of which were papillary carcinoma. Only 21 cases of squamous cell carcinoma arising in a thyroglossal duct cyst have been reported. The present case is the first report of adenosquamous carcinoma arising in a thyroglossal duct cyst.

High-grade surface osteosarcoma of the hand.

A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method

We developed an easy, quick and cost‐effective detection method for lymph node metastasis called the semi‐dry dot‐blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti‐pancytokeratin antibody, modifying dot‐blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node‐negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2‐mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis.

Primary cardiac osteosarcoma with imaging that revealed no calcification.

Osteosarcoma is a rare primary cardiac malignancy. Calcification on imaging is crucial to differentiating osteosarcoma, but we encountered a case that was difficult to diagnose because imaging revealed no calcification. A 67-year-old man was admitted for heart failure. Echocardiography demonstrated mitral regurgitation and a mass in the left atrium. A cardiac malignancy was suspected. Computed tomography revealed no calcification. Operation was performed, and histopathological examination identified the tumor as an osteosarcoma.

Eosinophilic Granulomatosis With Polyangiitis With Thrombotic Microangiopathy: Is Simultaneous Systemic Lupus Erythematosus Associated With Clinical Manifestations?: A Case Report and Review of the Literature.

AbstractEosinophilic granulomatosis with polyangiitis (EGPA) is one of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which is characterized by vasculitis of the small to medium-sized vessels. On the contrary, thrombotic microangiopathy (TMA) is a life-threatening condition which can cause ischemic organ injury. Although several case reports have described patients with TMA associated with ANCA-associated vasculitis except for EGPA, there are no previous case reports of EGPA associated with TMA.A 71-year-old Japanese man was diagnosed with EGPA based on his asthma, eosinophilia, lung opacity, refractory sinusitis, and positive myeloperoxidase-ANCA. He was also diagnosed with TMA based on peripheral schizocytes and hemolytic anemia. We performed plasmapheresis and started high-dose corticosteroid therapy; thereafter, he improved promptly. His case also fulfilled the classification criteria of systemic lupus erythematosus (SLE) based on the pleural effusion, renal disorder, anemia, thrombocytopenia, positive antidouble-stranded DNA antibody, and low complement. Elements of SLE were thought to affect his clinical course.We reviewed 11 patients with EGPA or hypereosinophilic syndrome (HES) associated with SLE, including our case. Patients with EGPA or HES associated with SLE had more heart complications than patients with simple EGPA or simple HES did. Patients with EGPA or HES associated with SLE had more pleural effusion than patients with simple SLE did.Clinical manifestations of eosinophilia with SLE or SLE with eosinophilia may differ from simple SLE or simple eosinophilia.

Solitary Fibrous Tumor Arising from the Sphenoid Sinus

Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. To our knowledge, only 30 cases of SFTs in the nasal cavity and paranasal sinuses have been reported in the literature. We describe an SFT that arose from the right sphenoid sinus and extended to the nasal cavity and epipharynx. The tumor was completely removed by endoscopic sinus surgery without complication. The patient is taking an uneventful course without any evidence of recurrence of the disease 8 months after surgery now.

Aggressive Pulmonary Calcification Developed After Living Donor Kidney Transplantation in a Patient With Primary Hyperparathyroidism

Metastatic pulmonary calcification, defined as calcium deposition in the intact lung, is commonly seen in patients with chronic renal failure, and it is known to be a benign clinical condition when detected by chance in an asymptomatic patient. Here we report the case of a 33-year-old woman who developed rapid and aggressive metastatic pulmonary calcification shortly after a living donor kidney transplantation, which induced acute antibody-mediated rejection. The patients metastatic pulmonary calcification was successfully improved by extensive treatment for graft rejection, the correction of her accompanying primary hyperparathyroidism, and medical treatment with a bisphosphonate and sodium thiosulfate. Aggressive pulmonary calcification is reported as a rare complication seen in patients who have undergone a failed renal transplantation. A failed renal graft and accompanying secondary hyperparathyroidism seem to accelerate metastatic calcification. Most of the patients who develop aggressive pulmonary calcification suffer from the rapid progression of dyspnea and occasionally fever, and they die of respiratory failure. Pulmonary calcification should be considered in a patient developing dyspnea and unexplained pulmonary infiltrate, especially in the context of renal graft rejection; otherwise the prognosis of the patient will be very poor.