Toshio Kumasaka

Prevalence of Uterine and Adnexal Involvement in Pulmonary Lymphangioleiomyomatosis: A Clinicopathologic Study of 10 Patients

Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3–positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.

Characterization of pulmonary cysts in Birt–Hogg–Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients

To characterize the pathological features of pulmonary cysts, and to elucidate the possible mechanism of cyst formation in the lungs of patients with Birt–Hogg–Dubé syndrome (BHDS), a tumour suppressor gene syndrome, using histological and morphometric analyses.

A Total Pleural Covering for Lymphangioleiomyomatosis Prevents Pneumothorax Recurrence

Background Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. Methods Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. Results TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%). Conclusions TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment.

Histological analysis of vasculopathy associated with pulmonary hypertension in combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis or emphysema alone

To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema (CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis (IPF) alone and emphysema alone.

Immunohistochemical analysis of thoracic endometriosis.

Thoracic endometriosis is a rare disease responsible for catamenial pneumothorax. The immunohistochemical features of thoracic endometriosis are not well understood. An immunohistochemical examination of 84 diaphragmatic specimens of catamenial pneumothorax using antibodies against estrogen receptor (ER), progesterone receptor (PgR), CD10 and smooth muscle actin (SMA) was conducted. The endometrial tissue was small, and focally located around the chasm of the tendon on the side of the thoracic cavity. Endometrial stroma were detected in 84/84 (100%) of the specimens, endometrial glands were detected in 21/84 (25%) and smooth muscle was detected in 1/84 (1.2%). The endometrial stroma exhibited positive staining for ER in 74/84 (88.1%) of the specimens, PgR in 84/84 (100%), CD10 in 74/84 (88.1%) and SMA in 46/84 (54.8%). Because thoracic endometriosis is small in size, and only 25% of the resected tissue specimens were accompanied with the endometrial gland, an immunohistochemical analysis can be useful for their detection. The fact that over half of the thoracic endometrial stroma showed positive staining for SMA, and the existence of thoracic endometriosis accompanied by smooth muscle, indicated that some part of the thoracic endometriosis may have the ability to differentiate into smooth muscle, although further studies are needed to confirm this hypothesis.

Efficacy and safety of stereotactic body radiotherapy using CyberKnife in Stage I primary lung tumor

Background CyberKnife® (CK) is a new, advanced radiotherapy technique. This study aimed to evaluate its efficacy and toxicity in Japanese patients with early-stage primary lung tumor who were medically unfit and inoperable. Methods This retrospective study investigated patients who received CK treatment for medically inoperable Stage І primary lung tumor at the Japanese Red Cross Medical Center between June 2011 and September 2016. Each patient received a total of 36-48 Gy (median, 43 Gy) administered by CK in 4-5 fractions. Results Totally, 40 patients (T1a, n = 19; T1b, n = 15; T2a, n = 6) were included. Their median age was 86 (range, 56-95) years. Tracking required the use of fiducial markers in 28 patients and the Xsight Spine Tracking System in 12. The median follow-up was 14.5 (range, 1-51) months. Local recurrence occurred in seven (17.5%) patients. The local progression-free survival rates at 1 and 2 years were 83.9% and 74.0%, respectively. Distant recurrence occurred in regional lymph nodes (n = 5), the lung outside the radiation field (n = 3), and the bone (n = 1). Seven patients died. Overall survival rates at 1 and 2 years were 93.6% and 73.1%, respectively. Radiation pneumonitis was identified in 28 (70%) patients (Grade 1, n = 25; Grade 2, n = 2; Grade 5, n = 1). Conclusions CK showed good local control with limited toxicity and could be an alternative treatment modality in medically inoperable patients with Stage І primary lung tumor.

A Case of Intratumoral Hemorrhage of Liver Metastasis from a Rectal Neuroendocrine Tumor

A 56-year-old healthy woman was referred to our hospital for abdominal pain. Contrast-enhanced computed tomography (CT) showed a 14-cm-diameter liver tumor with intratumoral hemorrhage. We performed emergent transcatheter arterial embolization. She was referred to hepatic surgeon (M.M.) for resection. Preoperative colonoscopy showed an elevated lesion measuring 2 cm in diameter that was pathologically diagnosed as a rectal neuroendocrine tumor (NET). We performed low anterior resection of the rectum, followed by extended right hepatectomy for all hepatic lesions. Intratumoral hematoma was observed in the largest hepatic lesion (size: 150 mm×100 mm). Microscopy also indicated NET G2. We pathologically diagnosed a liver tumor from a rectal NET that bled spontaneously.

The combination of EBUS-TBNA and the PAB antibody led to a successful treatment for lung cancer in a patient with asymptomatic sarcoidosis mimicking nodal metastasis

Correct staging of lung cancer is important for the selection of the best therapy, but discriminating between lymphadenopathy from lung cancer and from sarcoidosis by imaging examinations is difficult. Additionally, distinguishing lymphadenopathy of sarcoidosis from sarcoid reactions which are sometimes caused by lung cancer is difficult on imaging and pathological findings. A 73-year-old woman was diagnosed as lung cancer clinical T1bN3M0 stage ШB based on false-positive 18F-fluoro-2-deoxyglucose positron emission tomography uptake. Because the effects of chemotherapy were different between the lymphadenopathy and the primary lesion, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed and revealed sarcoidosis as the cause of the lymphadenopathy with using a specific monoclonal antibody against Propionibacterium acnes (PAB antibody). Accordingly, the stage was changed to clinical T1bN0M0 stage ІA, for which radical operation was performed. EBUS-TBNA should be performed aggressively when the effect of chemotherapy is different between lymphadenopathies and other lesions, and the PAB antibody can help to discriminate between sarcoidosis and sarcoid reactions caused by lung cancer. The combination of EBUS-TBNA and the PAB antibody is expected to be valuable in the definitive diagnosis of a lymphadenopathy for the staging of lung cancer.

Is hypothyroidism in idiopathic pleuroparenchymal fibroelastosis a novel lung-thyroid syndrome?

BACKGROUND Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare type of interstitial pneumonia characterized by fibroelastosis. Patients with IPPFE as well as idiopathic interstitial pneumonia often have autoimmune diseases, which sometimes coincide with hypothyroidism (HypoT). However, there have been no reports on the association between IPPFE and HypoT. The purpose of this study was to evaluate the correlation between IPPFE and HypoT. We also examined the pathological features of the thyroid glands from autopsied cases. METHODS Thirteen patients diagnosed with IPPFE from among 255 consecutive cases of idiopathic interstitial pneumonia were included in this study; pertinent data were obtained from our hospitals clinical library. We examined the prevalence of HypoT and compared the clinical, radiological, and pathological features between the patients with and those without HypoT. Histological analyses of the lungs and thyroid glands were performed in 4 and 3 cases, respectively. RESULTS HypoT was identified in 7 of 13 patients (53.8%). Sex, body mass index, survival time, and laboratory test results were not significantly different between patients with and those without HypoT. Radiological and pathological lung findings were similar between both groups of patients. Thyroid gland histology demonstrated perifollicular or interlobular fibrosis without inflammation in all three cases, including a euthyroid case. CONCLUSIONS Although we only analyzed a small number of IPPFE cases, HypoT was prevalent among all of them. Characteristic fibrosis in the thyroid gland was observed even in a euthyroid case. Therefore, patients with IPPFE may potentially have thyroid gland dysfunction through a common pathogenesis in both organs.

The Significant Antitumor Activity of Nivolumab in Lung Adenocarcinoma with Choriocarcinomatous Features

We report the case of a 60-year-old Japanese man with a metastatic brain tumor that caused ataxia. As a consequence of resection of a cerebellar tumor, the tumor was diagnosed as a poorly differentiated adenocarcinoma with choriocarcinomatous features. The patient underwent bronchoscopy, leading to a diagnosis of the same histology as the brain tumor. After the administration of first-line chemotherapy and maintenance therapy due to progressive disease, he was given nivolumab and obtained a partial response; however, 11-months later, computed tomography showed tumor progression. Our experience suggests that nivolumab has strong activity, even in patients with a rare form of lung cancer.