Semi-quantitative evaluation of chest computed tomography for coronavirus disease 2019 in a critical care unit: A case-control study.

The spread of abnormal opacity on chest computed tomography (CT) has been reported as a predictor of coronavirus disease 2019 (COVID-19) severity; however, the relationship between CT findings and prognosis in patients with severe COVID-19 remains unclear. The objective of this study was to evaluate the extent of abnormal opacity on chest CT and its association with prognosis in patients with COVID-19 in a critical care medical center, using a simple semi-quantitative method. This single-center case-control study included patients diagnosed with severe COVID-19 pneumonia who were admitted to a critical care center. The diagnosis of COVID-19 was based on positive results of a reverse transcription polymerase chain reaction test. All patients underwent non-contrast whole-body CT upon admission. Six representative axial chest CT images were selected for each patient to evaluate the extent of lung lesions. The percentage of the area involved in the representative CT images was visually assessed by 2 radiologists and scored on 4-point scale to obtain the bedside CT score, which was compared between patients who survived and those who died using the Mann-Whitney U test. A total of 63 patients were included in this study: 51 survived and 12 died after intensive treatment. The inter-rater reliability of bedside scores between the 2 radiologists was acceptable. The median bedside CT score of the survival group was 12.5 and that of the mortality group was 16.5; the difference between the 2 groups was statistically significant. The degree of opacity can be easily scored using representative CT images in patients with severe COVID-19 pneumonia, without sophisticated software. A greater extent of abnormal opacity is associated with poorer prognosis. Predicting the prognosis of patients with severe COVID-19 could facilitate prompt and appropriate treatment.

Altered white matter microstructure and neurocognitive function of HIV-infected patients with low nadir CD4.

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects.

Effect of uterine position and intrapelvic motions on the image quality of 3D T2-weighted MRI of the uterus: Can short prescans predict the non-diagnostic image quality?

PURPOSE: To evaluate prescan findings of uterine position and intrapelvic motions that predict the non-diagnostic image quality of three-dimensional T2-weighted MRI (3D-T2WI) of the uterus. METHODS: This retrospective study included 287 women who underwent pelvic MRI including 3D-T2WI and short prescans consisting of 2D-T2WI and cine imaging. One radiologist classified 3D-T2WI of the uterus as being of diagnostic or non-diagnostic image quality and evaluated the prescans regarding uterine position and intrapelvic motions. Multivariate logistic regression analysis was performed to identify predictors of non-diagnostic 3D-T2WI. The predictive ability of the prescans was verified by two independent MRI technologists. RESULTS: Non-diagnostic 3D T2WI was found in 42 patients (14.6 %) and was significantly associated with severe motions of urinary flow in the bladder (p < 0.001), small bowel (p = 0.039), and respiration (p < 0.001). In the multivariate analysis of uterine position and intrapelvic motions, risk factors for the non-diagnostic image quality were prominent urinary flow when the uterus contacted the bladder (p < 0.001, adjusted odds ratio = 35.1) and severe respiratory and small bowel motions when the uterus was surrounded by the bowel (p < 0.001, adjusted odds ratio = 68.4). No risk factors were found for the uterus contacting the vertebrae. With these predictors, the prescans demonstrated a sensitivity of 82.9 and 68.3 %, and specificity of 88.2 and 93.9 % for the non-diagnostic 3D-T2WI by the two technologists, respectively. CONCLUSION: Intrapelvic motions have a different effect on the image quality of 3D-T2WI depending on the uterine position, and short prescans may be useful in predicting time-consuming non-diagnostic 3D-T2WI of the uterus.

Neurocognitive impairment and gray matter volume reduction in HIV-infected patients.

Although neuropsychological studies of human immunodeficiency virus (HIV)-infected patients have demonstrated heterogeneity in neurocognitive impairment and neuroimaging studies have reported diverse brain regions affected by HIV, it remains unclear whether individual differences in neurocognitive impairment are underpinned by their neural bases. Here, we investigated spatial distribution patterns of correlation between neurocognitive function and regional gray matter (GM) volume across patients with HIV. Thirty-one combination antiretroviral therapy-treated HIV-infected Japanese male patients and 33 age- and sex-matched healthy controls were included in the analysis after strict exclusion criteria, especially for substance use. Fifteen neurocognitive tests were used, and volumetric magnetic resonance imaging was performed. We used voxel-based morphometry to compare GM volume between groups and identify regional GM volumes that correlated with neurocognitive tests across patients. Using the Frascati criteria, 10 patients were diagnosed with asymptomatic neurocognitive impairment, while the others were not diagnosed with HIV-associated neurocognitive disorders. Patients showed a significantly lower performance in five neurocognitive tests as well as significantly reduced GM volume relative to controls, with volume-reduced regions spread diffusely across the whole brain. Different aspects of neurocognitive impairment (i.e., figural copy, finger tapping, and Pegboard) were associated with different GM regions. Our findings suggest a biological background constituting heterogeneity of neurocognitive impairment in HIV infection and support the clinical importance of considering individual differences for tailor-made medicine for people living with HIV.

Comparison of HASTE with multiple signal averaging versus conventional turbo spin echo sequence: a new option for T2-weighted MRI of the female pelvis.

OBJECTIVES: This study was conducted in order to evaluate the feasibility of a newly developed half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence for T2-weighted MRI of the female pelvis, in which scanning and post-processing filtering techniques were optimized to minimize blurring and the resultant reduction in signal-to-noise ratio (SNR) was compensated by signal averaging of multiple excitations (multi-NEX), and to compare its image quality with that of a conventional turbo spin echo (TSE) sequence. METHODS: Fifty females with gynecological disease were prospectively enrolled. They underwent pelvic MRI including sagittal T2-weighted imaging obtained with multi-NEX HASTE (mHASTE) and TSE with acquisition times of 1 m 9 s and 3 m 26 s, respectively. At the prospective reading, mHASTE was reviewed first, and any changes in the image interpretation detected during the subsequent TSE reading were recorded. The SNR and tissue contrast were quantitatively measured. Two radiologists independently assessed tissue conspicuity and overall image quality considering noise, artifacts, and blurring, and visual grading characteristics (VGC) analysis was performed to compare the two sequences. RESULTS: Adding TSE to mHASTE did not change image interpretations in any case. mHASTE produced an equivalent SNR and significantly higher contrast between the myometrium and junctional zone (p < 0.05) compared with TSE. The area under the VGC curve (AUCVGC) showed that the conspicuity of the uterus, ovaries, and lesions and the overall image quality were significantly higher on mHASTE than on TSE for both readers (AUCVGC, 0.740-0.880; p < 0.01). CONCLUSION: mHASTE is a feasible option for T2-weighted MRI of the female pelvis, as it allows faster and higher-quality image acquisition than conventional TSE. KEY POINTS: • High-quality T2-weighted imaging is essential for magnetic resonance imaging of the female pelvis. • A new HASTE sequence was developed, in which a parallel imaging technique, a wide bandwidth, and a post-processing filter were used to minimize blurring, and the resultant reduction in the signal-to-noise ratio was compensated using signal averaging of multiple excitations (multi-NEX). • Multi-NEX HASTE allows fast and high-quality T2-weighted image acquisition.

Computed tomography-guided preoperative localization of small lung nodules with indocyanine green.

Background Small, deep-seated lung nodules and sub-solid nodules are often difficult to locate without marking. Purpose To evaluate the success and complication rates associated with the use of indocyanine green (ICG) to localize pulmonary nodules before resection. Material and Methods This retrospective study was approved by our institutional review board. Informed consent for performing preoperative localization using ICG marking was obtained from all patients. Thirty-seven patients (14 men, 23 women; mean age = 63.1 years; age range = 10-82 years) with small peripheral pulmonary nodules underwent computed tomography (CT)-guided ICG marking immediately before surgery between March 2007 and June 2016. The procedural details and complication rates associated with ICG marking are described. Results The average nodule size and depth were 9.1 mm (range = 2-22 mm) and 9.9 mm (range = 0-33 mm), respectively. Marking was detected at the pleural surface in 35 patients (95%). Three cases of mild pneumothorax (8%), five cases of cough (14%), and one case of mild bloody sputum (3%) with no clinical significance were noted. There were no severe complications. The average duration required to perform the marking was 19.4 min (range = 12-41 min). Conclusion Our results indicate that CT-guided ICG marking is safe and useful for detecting the location of small pulmonary nodules preoperatively.

Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma.

Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study.

INTRODUCTION: The purpose of this study was to evaluate the natural course of the progression of pulmonary subsolid nodules (SSNs). MATERIALS AND METHODS: Eight facilities participated in this study. A total of 795 patients with 1229 SSNs were assessed for the frequency of invasive adenocarcinomas. SSNs were classified into three categories: pure ground-glass nodules (PGGNs), heterogeneous GGNs (HGGNs) (solid component detected only in lung windows), and part-solid nodules. RESULTS: The mean prospective follow-up period was 4.3 ± 2.5 years. SSNs were classified at baseline as follows: 1046 PGGNs, 81 HGGNs, and 102 part-solid nodules. Among the 1046 PGGNs, 13 (1.2%) developed into HGGNs and 56 (5.4%) developed into part-solid nodules. Among the 81 HGGNs, 16 (19.8%) developed into part-solid nodules. Thus, the SSNs at the final follow-up were classified as follows: 977 PGGNs, 78 HGGNs, and 174 part-solid nodules. Of the 977 PGGNs, 35 were resected (nine minimally invasive adenocarcinomas [MIAs], 21 adenocarcinomas in situ [AIS], and five atypical adenomatous hyperplasias). Of the 78 HGGNs, seven were resected (five MIAs and two AIS). Of the 174 part-solid nodules, 49 were resected (12 invasive adenocarcinomas, 26 MIAs, 10 AIS, and one adenomatous hyperplasia). For the PGGNs, the mean period until their development into part-solid nodules was 3.8 ± 2.0 years, whereas the mean period for the HGGNs was 2.1 ± 2.3 years (p = 0.0004). CONCLUSION: This study revealed the frequencies and periods of development from PGGNs and HGGNs into part-solid nodules. Invasive adenocarcinomas were diagnosed only among the part-solid nodules, corresponding to 1% of all 1229 SSNs.

Oncologic Outcomes of Segmentectomy Versus Lobectomy for Clinical T1a N0 M0 Non-Small Cell Lung Cancer.

BACKGROUND: We retrospectively compared the oncologic outcome after segmentectomy versus lobectomy in patients with clinical (c-) T1a N0 M0 non-small cell lung cancer (NSCLC) detected as a part-solid ground-glass nodule or purely solid nodule on thin-section computed tomography. METHODS: From 1997 to 2010, 312 patients with c-T1a N0 M0 NSCLC were determined to require a surgical approach categorized as segmentectomy or lobectomy. Preoperatively available data were collected using logistic regression analysis, and propensity matching was performed. Factors affecting local-regional recurrence were assessed by Cox proportional hazards regression analysis and Kaplan-Meier estimates. RESULTS: The 5-year and 10-year overall survival rates for the 80 patients who underwent segmentectomy were 97.5% and 83.5%, respectively, compared with 87.75% and 75.0%, respectively, for the 232 patients who underwent lobectomy (p = 0.019). Local-regional recurrence as the first relapse site was found in 3 the 80 segmentectomies (3.8%) of and in 15 of the 232 lobectomies (6.5%). The difference in local-regional recurrence-free survival in patients undergoing segmentectomy compared with lobectomy was not significant (p = 0.304). In 69 propensity score-matched pairs, there was no significant difference in the overall survival (p = 0.442) or local-regional recurrence-free survival (p = 0.717) between the two groups. Multivariate analysis using the Cox proportional hazards regression model identified lymphatic invasion as the only independent factor predicting local-regional recurrence (relative risk, 10.764; 95% confidence interval, 2.98 to 57.68). CONCLUSIONS: Our results suggest that the oncologic outcome of segmentectomy vs lobectomy is similar in this cohort of c-T1a N0 M0 NSCLC patients. These results will be validated by large-scale, prospective, randomized trials.

Clinicopathological Factors Related to the Prognosis of Metastatic Breast Cancer Patients after Development of Brain Metastasis.

BACKGROUND: The prognosis of breast cancer patients with brain metastasis (BM) is extremely poor, and the survival after development of BM is very short. We aimed to investigate clinicopathological factors related to significant effects on the prognosis after BM development. PATIENTS AND METHODS: This is a retrospective study of 75 early breast cancer patients who received the standard of care and subsequently developed BM. RESULTS: Breast cancer subtype was one of the significant predictors for prognosis after BM diagnosis. Luminal HER2 patients had the most favorable prognosis after BM diagnosis (p = 0.011). Favorable performance status (PS) at BM diagnosis (p < 0.001) and a single metastatic brain tumor (p = 0.032) were significantly associated with good prognosis after BM diagnosis. Metastatic time courses of the patients was found not to be significantly associated with survival after BM diagnosis. Univariate and multivariate analysis indicated that luminal HER2 cancer, favorable PS at BM diagnosis, and a single metastatic brain tumor were the independent prognostic factors for survival after BM development, making a decisive influence on local or systemic control. CONCLUSION: Appropriate treatments for tumor subtypes and to improve the general condition of patients would result in improved outcomes for the patients with BM.

[Pulmonary metastasis of an ovarian granulosa cell tumor resected 11 years before].

A 69-year-old female, who had undergone oophorectomy for a left ovarian granulosa cell tumor (OGCT) in November 1999, was referred to our hospital due to rectal infiltration of the tumor detected during the initial surgery. The patient underwent low anterior resection, omentectomy and adnexectomy for the residual lesion at 1 month after the initial operation, and was followed up without postoperative adjuvant chemotherapy. In November 2010, abdominal computed tomography( CT) showed a soft tissue tumor on the surface of the liver. Meanwhile, a solitary nodule in S3 of the left lung was detected on chest CT. Laparotomy was done under suspicion of liver metastasis, but the lesion was revealed to be peritoneal dissemination at surgery. After subsequent 1-year follow-up, the enlargement of the pulmonary nodule was noted, and partial resection of the left lung was performed. The tumor was pathologically diagnosed as a metastasis of the OGCT.

Primary chest wall abscess mimicking a breast tumor that occurred after blunt chest trauma: a case report.

Primary chest wall abscess occurring after blunt chest trauma is rare. We present the case of a 50-year-old woman who presented with a swelling in her left breast. The patient had experienced blunt chest trauma 2 months back. Needle aspiration revealed pus formation in the patient's chest. Computed tomography revealed a mass in the lower region of the left mammary gland, with thickening of the parietal pleura and skin and fracture of the fifth rib under the abscess. Following antibiotic administration and irrigation of the affected region, surgical debridement was performed. During surgery, we found that the pectoralis major muscle at the level of the fifth rib was markedly damaged, although the necrotic tissue did not contact the mammary gland. We diagnosed the lesion as a chest wall abscess that occurred in response to blunt chest trauma. Her postoperative course was uneventful. There has been no recurrence for six months after surgery.

Tocotrienol (unsaturated vitamin E) suppresses degranulation of mast cells and reduces allergic dermatitis in mice.

In this study, we examined whether tocotrienol (T3) reduces allergic dermatitis in mice and suppresses degranulation of mast cells. First, allergic dermatitis was examined in the atopic dermatitis model NC/Nga mouse. Allergic dermatitis was induced using picryl chloride in mice with and without administration of T3 (1 mg/day/mouse). Increases in scratching behavior, dermal thickening, and the serum histamine level were greatly reduced in mice treated with T3, indicating that T3 reduces allergic dermatitis in vivo. Next, the effect of T3 on degranulation of mast cells was examined, since these cells release bioactive substances such as histamine. T3 significantly suppressed degranulation of mast cells and significantly reduced histamine release. The effect of T3 on protein kinase C (PKC) activity was also measured, since suppression of this activity may be associated with the mechanism underlying the antidegranulation effect of T3. T3 significantly suppressed PKC activity. Therefore, we conclude that T3 suppresses degranulation of mast cells and reduces allergic dermatitis in mice through reduction of PKC activity.

Radiologic implications of the 2011 classification of adenocarcinoma of the lung.

Now the leading subtype of lung cancer, adenocarcinoma received a new classification in 2011. For tumors categorized previously as bronchioloalveolar carcinoma (BAC), criteria and terminology had not been uniform, so the 2011 classification provided four new terms: (a) adenocarcinoma in situ (AIS), representing histopathologically a small (≤3-cm), noninvasive lepidic growth, which at computed tomography (CT) is usually nonsolid; (b) minimally invasive adenocarcinoma, representing histopathologically a small (≤3-cm) and predominantly lepidic growth that has 5-mm or smaller invasion, which at CT is mainly nonsolid but may have a central solid component of up to approximately 5 mm; (c) lepidic predominant nonmucinous adenocarcinoma, representing histopathologically invasive adenocarcinoma that shows predominantly lepidic nonmucinous growth, which at CT is usually part solid but may be nonsolid or occasionally have cystic components; and (d) invasive mucinous adenocarcinoma, histopathologically showing lepidic growth as its predominant component, which at CT varies widely from solid to mostly solid to part solid to nonsolid and may be single or multiple (when multifocal, it was formerly called multicentric BAC). In addition, new histopathologic subcategories of acinar, papillary, micropapillary, and solid predominant adenocarcinoma are now described, all as nonmucinous, predominantly invasive, may include a small lepidic component, and at CT are usually solid but may include a small nonsolid component. The micropapillary subtype has a poorer prognosis than the other subtypes. In addition, molecular genetic correlations for the subcategories of adenocarcinoma of the lung are now a topic of increasing interest. As the new classification enters common use, further descriptions of related correlations can be anticipated.

Male breast cancer originating in an accessory mammary gland in the axilla: a case report.

Carcinoma of an accessory mammary gland is an extremely rare tumor. A 61-year-old male patient presented with a hard mass measuring 85 mm × 51 mm in the left axilla. Incisional biopsy histopathologically showed an adenocarcinoma compatible with breast carcinoma originating in an accessory mammary gland. Systemic examinations revealed no evidence of malignant or occult primary lesion in the bilateral mammary glands or in other organs. Neoadjuvant chemotherapy was performed for the locally advanced axillary tumor and reduced the tumor to 55 mm in size, and, then, he could undergo complete resection with a negative surgical margin in combination with reconstructive surgery to fill the resulting skin defect with a local flap of the latissimus dorsi muscle. The patient has presented with no metastatic lesion in four years since the operation. This unusual case shows that neoadjuvant chemotherapy is an effective and tolerated therapy for advanced accessory breast cancer in the axilla.

[Micronodular thymoma with lymphoid stroma（MNT）].

We report a surgical case of MNT, which is a rare type of thymoma. A 56-year-old man was referred to our hospital for examination of a mass in the anterior mediastinum. The computed tomography (CT) scan showed a lobulated mass with relatively smooth margins. Also, contrast study indicated homogeneous enhancement. Since these findings suggested the possibility of thymoma, the patient underwent thymothymomectomy. Histological findings showed short spindleshaped tumor cells forming nests of various sizes, and lymphoid stroma with lymphoid follicles. The pathological diagnosis was MNT. The long-term outcome after resection of MNT currently remains unclear, and accumulation of further cases is required.

Measurement of focal ground-glass opacity diameters on CT images: interobserver agreement in regard to identifying increases in the size of ground-glass opacities.

PURPOSE: To evaluate interobserver agreement in regard to measurements of focal ground-glass opacities (GGO) diameters on computed tomography (CT) images to identify increases in the size of GGOs. MATERIALS AND METHODS: Approval by the institutional review board and informed consent by the patients were obtained. Ten GGOs (mean size, 10.4 mm; range, 6.5-15 mm), one each in 10 patients (mean age, 65.9 years; range, 58-78 years), were used to make the diameter measurements. Eleven radiologists independently measured the diameters of the GGOs on a total of 40 thin-section CT images (the first [n = 10], the second [n = 10], and the third [n = 10] follow-up CT examinations and remeasurement of the first [n = 10] follow-up CT examinations) without comparing time-lapse CT images. Interobserver agreement was assessed by means of Bland-Altman plots. RESULTS: The smallest range of the 95% limits of interobserver agreement between the members of the 55 pairs of the 11 radiologists in regard to maximal diameter was -1.14 to 1.72 mm, and the largest range was -7.7 to 1.7 mm. The mean value of the lower limit of the 95% limits of agreement was -3.1 ± 1.4 mm, and the mean value of their upper limit was 2.5 ± 1.1 mm. CONCLUSION: When measurements are made by any two radiologists, an increase in the length of the maximal diameter of more than 1.72 mm would be necessary in order to be able to state that the maximal diameter of a particular GGO had actually increased.

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

INTRODUCTION: Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. METHODS: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. CONCLUSIONS: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.