Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn.

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.

Efficacy of durvalumab plus chemotherapy in small-cell lung cancer with Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare disease but is often associated with small-cell lung cancer (SCLC). We discuss the case of a 65-year-old man diagnosed with SCLC-LEMS and treated with carboplatin, etoposide, and durvalumab. Lower extremity weakness and high anti-P/Q voltage-gated calcium channel (VGCC) antibody levels were diagnostic and helpful. The patient showed a reduction in neurological symptoms with treatment for SCLC, including an immune checkpoint inhibitor (ICI), without standard treatment for LEMS. This treatment may be a treatment option, although the recurrence of LEMS as an immune-related adverse events (irAEs) should be noted.

Factors associated with cavity formation after stereotactic body radiation therapy for peripheral early-stage lung cancer.

PURPOSE: This retrospective study aimed to identify the factors associated with cavity formation after SBRT in peripheral early-stage lung cancer patients. We analyzed the occurrence of cavity changes after SBRT. MATERIALS AND METHODS: We examined 99 cases with T1-T2aN0 peripheral non-small cell lung cancer treated with SBRT from 2004 to 2021. Patients underwent respiratory function tests, including diffusing capacity for carbon monoxide (DLco), before treatment. The median observation period was 35 months (IQR 18-47.5 months). Treatment involved fixed multi-portal irradiation in 67% of cases and VMAT in 33%. The total radiation doses ranged from 42 to 55 Gy, delivered over 4 to 5 fractions. RESULTS: Cavity formation occurred in 14 cases (14.1%), appearing a median of 8 months after SBRT. The cavity disappeared in a median of 4 months after formation. High DLco and total radiation dose were identified as factors significantly associated with cavity formation. There have been no confirmed recurrences to date, but one patient developed a lung abscess. CONCLUSION: Although cavity formation after SBRT for peripheral early-stage lung cancer is infrequent, it can occur. This study showed high DLco and total radiation dose to be factors significantly associated with cavity formation. These findings can be applied to optimizing radiation therapy (RT) and improving patient outcomes. Further research is needed to determine the optimal radiation dose for patients with near-normal DLco for whom surgery is an option. This study provides valuable insights into image changes after RT.

First case report of erlotinib plus ramucirumab treatment for lung carcinosarcoma with EGFR L858R mutation.

Lung carcinosarcoma is acknowledged as a rare form of lung cancer. Due to its rarity, the inability to conduct large-scale clinical trials and interventions is currently carried out based on empirical evidence. In this study, we report the case of a 73-year-old female patient diagnosed with postoperative recurrence of lung carcinosarcoma. The resected tumor was diagnosed as lung carcinosarcoma, and genetic testing revealed the presence of the epidermal growth factor receptor (EGFR) exon21 L858R. Approximately 2 years postoperatively, the tumor recurred and the patient was treated with erlotinib plus ramucirumab, which were effective in controlling metastatic disease. Erlotinib plus ramucirumab is therefore a treatment option for EGFR mutation-positive lung carcinosarcoma.

Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery.

BACKGROUND: Administration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa. METHODS: This study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT. RESULTS: During salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR. CONCLUSION: This is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.

Relationship between Laser Intensity at the Peripheral Nerve and Inhibitory Effect of Percutaneous Photobiomodulation on Neuronal Firing in a Rat Spinal Dorsal Horn.

Photobiomodulation is an effective treatment for pain. We previously reported that the direct laser irradiation of the exposed sciatic nerve inhibited firing in the rat spinal dorsal horn evoked by mechanical stimulation, corresponding to the noxious stimulus. However, percutaneous laser irradiation is used in clinical practice, and it is unclear whether it can inhibit the firing of the dorsal horn. In this study, we investigated whether the percutaneous laser irradiation of the sciatic nerve inhibits firing. Electrodes were inserted into the lamina II of the dorsal horn, and mechanical stimulation was applied using von Frey filaments (vFFs) with both pre and post laser irradiation. Our findings show that percutaneous laser irradiation inhibited 26.0 g vFF-evoked firing, which corresponded to the noxious stimulus, but did not inhibit 0.6 g and 8.0 g vFF-evoked firing. The post- (15 min after) and pre-irradiation firing ratios were almost the same as those for direct and percutaneous irradiation. A photodiode sensor implanted in the sciatic nerve showed that the power density reaching the sciatic nerve percutaneously was attenuated to approximately 10% of that on the skin. The relationship between the laser intensity reaching the nerve and its effect could be potentially useful for a more appropriate setting of laser conditions in clinical practice.

Near-Infrared Photobiomodulation of the Peripheral Nerve Inhibits the Neuronal Firing in a Rat Spinal Dorsal Horn Evoked by Mechanical Stimulation.

Photobiomodulation has analgesic effects via inhibition of nerve activity, but few reports have examined the effects on the spinal dorsal horn, the entry point for nociceptive information in the central nervous system. In this study, we evaluated the effects of laser irradiation of peripheral nerve axons, which are conduction pathways for nociceptive stimuli, on the neuronal firing in lamina II of the spinal dorsal horn of a rat evoked by mechanical stimulation with von Frey filaments (vFF). In order to record neuronal firing, electrodes were inserted into lamina II of the exposed rat spinal dorsal horn. The exposed sciatic nerve axons were irradiated with an 808 nm laser. The 26.0 g vFF-evoked firing frequency was inhibited from 5 min after laser irradiation and persisted for 3 h. Sham irradiation did not alter the firing frequency. Laser irradiation selectively inhibited 15.0 and 26.0 g vFF-evoked firing, which corresponded to nociceptive stimuli. Histopathological evaluation revealed no damage to the sciatic nerve due to laser irradiation. These results indicate that neuronal firing is inhibited in lamina II of the spinal dorsal horn, suggesting that laser irradiation inhibits Aδ and/or C fibers that conduct nociceptive stimuli.

Bone scan index on bone scintigraphy and radiation therapy for bone metastases from cancers other than prostate and breast cancers: A retrospective observational study.

Objective: In this study, we aimed to use new automatic analysis software (VSBONE bone scan index (BSI); Nihon Medi-Physics, Tokyo, Japan) to investigate whether the pre-radiation therapy (RT) BSI, derived from bone scintigraphy (BS) images, is a prognostic indicator in patients undergoing RT for bone metastases from cancers other than breast or prostate cancer. Materials and Methods: In this retrospective single-institution study, we analyzed data of 51 patients who had undergone whole-body scintigraphy before receiving RT for bone metastases from cancers other than breast and prostate cancer between 2013 and 2019. Their bone metastases preradiation BSI were automatically calculated using newly developed software (VSBONE BSI; Nihon Medi-Physics, Tokyo, Japan). Univariate and multivariate analyses were performed to identify associations between selected clinical variables and overall survival (OS). Results: We did not find a significant association between BSI and OS. However, we did find that younger patients had significantly better OS than older patients (P = 0.016 and P = 0.036, respectively). In addition, BSI were significantly lower in patient with solitary or osteolytic bone metastases than in those with osteoblastic or mixed bone metastases (P = 0.035 and P ≤ 0.001, respectively), and significantly higher in those with lung cancer than in those with other types of cancer (mean BSI 3.26% vs. 1.97%; P = 0.009). Conclusion: The only significant association with survival identified in this study was for age at the time of BS and at time of diagnosis of bone metastases.

Prediction of Postoperative Respiratory Complications after Lobectomy in Lung Cancer Patients with COPD by Quantitative Image Analysis: A Historical Cohort Study.

PURPOSE: We examined whether preoperative assessment of percentage of low attenuation area (LAA%) on the non-resected side can predict postoperative respiratory complications (PRC) after lobectomy. MATERIALS AND METHODS: We conducted a historical cohort study of 217 smokers (175 males and 42 females) who underwent lobectomy for primary lung cancer at our hospital between January 2014 and March 2021. First, the relationship between LAA% and respiratory function parameters (RFPs) calculated for both the bilateral and non-resected sides was used to estimate the most effective patient group. Next, multivariate analyses of the relationship between LAA% of the non-resected side and PRC were performed using logistic regression analysis after adjusting for basic patient attributes and respiratory function. RESULTS: A correlation was found between LAA% and RFP in smoking males. Multivariate analysis showed a strong relationship between model 3, adjusted for basic patient attributes and lung function factors, and PRC (odds ratio, 2.43; 95% confidence interval, 1.05-5.63). CONCLUSION: LAA% of the non-resected side suggested that it may be able to predict the occurrence of PRC after lung cancer lobectomy.

Coronavirus disease 2019 (COVID-19) in patients before, during, or after lung irradiation, and serum SP-A and SP-D levels.

BACKGROUND: The correlation between COVID-19 and RT has not been determined to date and remains a clinical question. The aim of this study was to evaluate coronavirus disease 2019 (COVID-19) pneumonia before, during, and after radiation therapy (RT) regarding the radiation doses, radiation pneumonitis, and surfactant protein levels. METHODS: We evaluated patients diagnosed with COVID-19 before, during, or after RT for the lung between August 2020 and April 2022. In patients with breast cancer, the RT dose to the ipsilateral lung was determined. In all other patients, bilateral lung RT doses were determined. Patients diagnosed with COVID-19 after RT were evaluated to determine whether radiation pneumonitis had worsened compared with before RT. The serum levels of the surfactant proteins SP-A and SP-D were measured before, during, and after RT. RESULTS: The patients included in the study comprised three men (27.3%) and eight women (72.7%). The primary cancer sites were the breast (n = 7; 63.7%), lung (n = 2; 18.1%), esophagus (n = 1; 9.1%), and tongue (9.1%). COVID-19 was diagnosed before RT in four patients, during RT in two patients, and after RT in five patients. Six (54.5%) patients developed COVID-19 pneumonia. Radiation pneumonitis grade ≥2 was not identified in any patient, and radiation pneumonitis did not worsen after RT in any patient. No rapid increases or decreases in SP-A and SP-D levels occurred after the diagnosis of COVID-19 in all patients regardless of RT timing. CONCLUSIONS: COVID-19 did not appear to result in lung toxicity and surfactant protein levels did not change dramatically.

The impact of lymphadenectomy on lymph node recurrence after performing various treatments for esophageal squamous cell carcinoma.

BACKGROUND: Treatment for regional lymph node recurrence after initial treatment for esophageal squamous cell carcinoma (ESCC) differs among institutions. Though some retrospective cohort studies have shown that lymphadenectomy for cervical lymph node recurrence is safe and leads to long-term survival, the efficacy remains unclear. In this study, we investigated the long-term outcomes of patients who underwent lymphadenectomy for regional recurrence after treatment for ESCC. PATIENTS AND METHODS: We retrieved 20 cases in which lymphadenectomy was performed for lymph node recurrence after initial treatment for ESCC in our hospital from January 2003 to December 2016. Initial treatments included esophagectomy, endoscopic resection (ER) and chemoradiotherapy/chemotherapy (CRT/CT). Overall survival (OS) and recurrence-free survival (RFS) after lymphadenectomy were calculated by the Kaplan-Meier method. We also used a univariate analysis with a Cox proportional hazards model to determine factors influencing the long-term outcomes. RESULTS: The five-year OS and RFS of patients who underwent secondary lymphadenectomy for recurrence after initial treatment were 50.0% and 26.7%, respectively. The five-year overall survival rates of patients who received esophagectomy, ER and CRT/CT as initial treatments, were 40.0%, 75.0% and 50.0%, respectively. The five-year OS rates of patients with Stage I and Stage II-IVB at initial treatments were 83.3% and 33.3%, respectively. CONCLUSIONS: Lymphadenectomy for regional recurrence after initial treatment for ESCC is effective to some degree. Patients with regional recurrence after initial treatment for Stage I ESCC have a good prognosis; thus, lymphadenectomy should be considered for these cases.

Reirradiation for recurrent head and neck carcinoma using high-dose-rate brachytherapy: A multi-institutional study.

AIM: This study presents multi-institutional individual data of reirradiation (ReRT) for head and neck cancer using brachytherapy (ReRT-BT) collected by national surveillance in Japan. METHODS AND MATERIALS: We distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate (HDR) brachytherapy facilities and received responses from 76 institutions (49.7%). Of these 76 institutions, only four (5.2%) performed ReRT-BT for head and neck cancers, and three provided individual patient's data. RESULTS: Six ReRT-BT cases of patients with recurrent head and neck cancer, treated with HDR brachytherapy in seven ReRT sessions, were identified from three institutions. Three patients (two cases of lips and one case of gingiva) who underwent curative-intent treatment achieved complete response at the treated area. Three patients who received palliative treatment (one case of tongue and two cases of maxillary sinus) had sustained tumor growth at the treated site, but with improvement in symptoms. No grade ≥3 toxicity was found after HDR ReRT-BT. CONCLUSIONS: ReRT-BT for head and neck cancer using HDR brachytherapy is a safe and useful approach to treat recurrent cancer after initial radiotherapy with curative and palliative intent. However, the scarce availability of ReRT-BT is a barrier to the wider utility of this effective procedure.

Radiation therapy for pelvic recurrent colorectal or gynecological cancer: is whole pelvic irradiation necessary?

BACKGROUND: Preoperative whole pelvic radiation therapy (RT) is used commonly for rectal cancer and is the standard field postoperatively in gynecological cancer. However, the ideal field (local vs. whole pelvis) has not been determined for local recurrence of these cancers. METHODS: We retrospectively reviewed the data for 52 patients who developed local tumor recurrence of rectal or gynecological cancer treated from 2013 to 2021. The initial treatment for all patients was total excision of the primary tumors without radiation therapy. Radiation therapy targets were surgical stumps, perianastomosis sites, and pelvic lymph nodes, classified according to the pelvic nodal volume atlas for radiation therapy. Patients were divided into the local recurrent tumor only radiation therapy group and the whole pelvis radiation therapy group. Whole pelvis radiation therapy included the common iliac lymph nodes or prophylactic lymph nodes below the L5/S1 junction. We recorded second recurrence after RT and the affected site(s) in each group. We also compared disease-specific survival using uni- and multivariate analyses. RESULTS: We found no significant differences between the groups regarding second recurrence or regarding the site(s) of recurrence. We also found no significant differences in disease-specific survival between the two RT groups. However, patients who did not receive chemotherapy after the initial surgery and before RT had significantly longer survival (P=0.015). CONCLUSIONS: In patients with locally recurrent rectal or gynecological cancer, we found no significant difference in second recurrence or survival between the local tumor only RT field and the whole pelvic RT field.

Coexistence of carcinoid tumor and adenocarcinoma of the lung; morphological, immunohistochemical and genetic analyses, a case report.

BACKGROUND: Pulmonary carcinoid tumors rarely coexist with non-small cell lung carcinoma, and only nine cases have been reported previously. The pathogenesis and origin of these combined tumors remain unclear because of its rarity. CASE PRESENTATION: We examined two cases of adenocarcinoma coexisting with a typical or atypical carcinoid tumor: Case 1 was a 77-year-old woman and Case 2 was an 83-year-old woman. Both of these cases had no respiratory symptoms, and underwent pulmonary lobectomies due to incidentally detected lung nodules. Recurrence and metastases were not detected after the surgery. Histologically, carcinoid and adenocarcinoma components were present in both cases. The two components coexisted without mixing with each other. Next-generation sequencing was performed on the two components in these cases. In each case, no common genetic variants were detected. CONCLUSION: We considered that our cases could histologically and genetically represent collision tumors that did not share common progenitor cells. Comprehensive analyses such as whole genome sequencing could provide important information for elucidating the pathogenesis of adenocarcinoma and carcinoid components.

Bladder filling volume variation between the first and second day of planning computed tomography for prostate cancer radiation therapy and correlation with renal function.

AIM: During radiation therapy (RT) for prostate cancer, bladder filling helps exclude the organ from irradiation and reduces adverse effects. For RT planning, we performed computed tomography (CT) for 2 consecutive days to evaluate inter-day variations in organs such as the bladder. However, the patient factors that are associated with large intra-patient variations in bladder filling volume prior to RT are not known. METHODS: This was a retrospective study of 97 prostate cancer patients who underwent CT for 2 consecutive days for RT planning between March 2015 and March 2020 and with confirmed water intake volume before the scans. Patients consumed 500 ml of water immediately after urination and underwent CT 30 min after the start of water intake; CT was performed under similar conditions over 2 consecutive days. Patient information was collected from the medical records taken before CT. RESULTS: The median bladder filling volume was 102.8 cm3 (range: 31.7-774.0), and the median intra-patient bladder filling volume variation was 23.4 cm3 (range: 0.4-277.7). Univariate analysis revealed that the intra-patient variation was significantly larger in patients with an eGFR higher than the median (p = 0.003). No other factor showed correlations with the variation. As the larger bladder filling volume of the 2 consecutive days in patients increased (median 121.5 cm3 , range: 47.8-774.0), the intra-patient variation also increased. CONCLUSION: Patients with a higher eGFR show greater variation in bladder filling volume, and caution should be exercised when applying RT in these patients.

Novel detection of the CAMTA1-WWTR1 fusion gene in extra-adrenal myelolipoma-like lesion: a case report.

A mediastinal mass was incidentally detected by chest X-ray in a 44-year-old man. Computed tomography findings revealed that the mass was a possible malignancy in the right and middle mediastinum and was removed by surgical resection. Macroscopically, the resected specimen was a well-demarcated yellowish, brownish, and whitish mass. Microscopically, a solid lesion with cords of epithelioid cells in the extra-adrenal myelolipoma-like lesion was observed. Immunohistochemically, the solid lesion was positive for typical vascular markers and CAMTA1, the expression of which is highly specific for epithelioid hemangioendothelioma (EHE). The endothelial cells and bone marrow elements of myelolipoma-like lesion were also positive for CAMTA1. Fluorescence in situ hybridization examination detected the CAMTA1-WWTR1 fusion gene not only in the solid lesion but also in the endothelial cells and bone marrow elements of myelolipoma-like lesion. To our knowledge, this is the first report suggesting common genetic abnormality, CAMTA1-WWTR1 fusion, in cases of EHE and extra-adrenal myelolipoma.

Bladder mucosa-associated lymphoid tissue lymphoma progressed from chronic cystitis along with a comparative genetic analysis during long-term follow-up: a case report.

The pathogenesis of bladder marginal zone/mucosa-associated lymphoid tissue (MALT) lymphoma, which is the most common type of primary bladder lymphoma, has not been clarified. There are no reports that described histological and molecular time course of MALT lymphoma occurring in the bladder and the importance of the score on the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale during and after radiation therapy (RT). We present a case of MALT lymphoma with long-term comparative genetic analysis. A 77-year-old Japanese woman with hematuria and severe perineal pain was found to have a tumor-like lesion in the bladder trigone. She was diagnosed with cystitis based on the results of pathological examination and immunostaining after transurethral resection of the lesion. The second transurethral resection procedure was performed approximately 4 years after the first procedure because of recurrence of the hematuria and enlargement of a lesion in the left bladder wall. Postoperative pathologic examination confirmed a diagnosis of MALT lymphoma. Genetic analysis of immunoglobulin heavy chain (IGH) gene rearrangements showed more clonal progression from the first biopsy to the second. The patient then underwent RT, during which her perineal pain was exacerbated by radiation cystitis but finally decreased to a level less severe than that before treatment. The PUF patient symptom scale was useful to monitor her pain throughout the clinical course. No recurrence was detected more than 2 years after completion of RT.

Non-contact and direct electrocaloric effect measurement for high-throughput material screening.

A non-contact and direct electrocaloric effect (ECE) measurement system was developed for rapid ECE measurement. The ECE of ferroelectric materials was measured directly using two measurement methods, namely, the constant heating rate method (CH method) and one-dimensional temperature gradient method (1D method), with the measurement system. The CH method continuously measures the ECE while gently heating the sample, and it can evaluate the performance of the sample more quickly than conventional methods that measure the ECE at steady state. The 1D method directly measures the ECE using a 1D temperature distribution applied to the sample. This method can measure the temperature dependence of the ECE faster than the CH method. The measurement system achieved a high signal-to-noise ratio, and the temperature dependence of the ECE measured by the two methods was consistent. The proposed measurement system and methods enable promising candidate materials for electrocaloric cooling systems to be screened more rapidly than when using conventional approaches.

Whole-brain Radiation Therapy for Intracranial Metastases as Initial or Late Treatment.

BACKGROUND/AIM: We examined the difference between whole-brain radiation therapy (WBRT) for intracranial metastases (IM) from lung cancer as an initial and as a late treatment affecting overall survival (OS). PATIENTS AND METHODS: Thirty-three patients who presented with IM at initial examination who received WBRT as the initial treatment (initial WBRT group) and 47 patients without IM or with asymptomatic IM at initial examination who received WBRT after systemic therapy, between January 2014 and December 2020, were retrospectively analyzed. Patients' OS after WBRT were compared. RESULTS: Median OS was significantly longer in patients treated with systemic anticancer therapy after WBRT than in patients who were not (176 vs. 47 days, respectively; p<0.001), and systemic anticancer therapy after WBRT was a significant prognostic factor (p<0.001). CONCLUSION: Treatment with systemic anticancer therapy after WBRT may prolong the survival of patients who present with IM at initial examination.

A Solitary Necrotizing Sarcoid Granulomatosis-like Pulmonary Lesion Possibly Associated with Propionibacterium acnes and Mycobacterium avium.

We report a case of a pulmonary necrotizing sarcoid granulomatosis (NSG)-like lesion possibly associated with coinfection of Mycobacterium avium and Propionibacterium acnes. A solitary nodule in the right middle lobe of the lung was notable for coagulative necrosis with aggregates of sarcoid-like epithelioid granulomas. Small arteries were damaged by granulomas. Both M. avium and P. acnes were detected in the lesion. Furthermore, more P. acnes genomes were detected in the granulomas than in the non-lesion lung. These findings blur the pathophysiologic boundaries among NSG, sarcoidosis, and mycobacteriosis, and suggest that NSG needs to be recognized as continuous spectra of sarcoidosis/mycobcteriosis.