Pathogenesis of Gastrointestinal Follicular Lymphomas: Consideration Based on Histopathology and Endoscopic Findings.

Gastrointestinal (GI) follicular lymphoma (FL) is the most frequently diagnosed extranodal FL; however, its pathogenesis is debatable. We investigated the distribution, endoscopic, and histopathologic findings of 366 GI FL samples obtained from 298 patients. FLs were most frequently observed in the small intestine (71%), including the duodenum (52%), but were also commonly found in the stomach (15%) and colon (12%). The proportion of granular lesions in the duodenum, terminal ileum, colon, and stomach was 74%, 39%, 24%, and 0%, respectively. Submucosal or ulcerated tumors were frequently observed in the stomach (48%) and colon (52%). Most GI FL showed grade 1 to 2 histology (89%) as well as CD10 + (93%) and BCL2 + (98%) positivity. There were no significant differences in the endoscopic or histologic findings between primary and secondary GI FLs. As known, the mucosa of the small intestine is thin and villous, while the mucosa of the stomach and colon is thicker and has a smooth surface. Granular lesions corresponding to very small FL were detected in the former but rarely in the latter. Nine (7%) patients with primary GI FL developed histologic transformation to diffuse large B-cell lymphoma (n=8) or high-grade B-cell lymphoma (n=1) 10 months to 14 years after the diagnosis of FL. Two patients died of lymphoma. In conclusion, the incidence and endoscopic findings differed, but the histopathology was similar in FLs in each site. These differences might be attributed to variations in each GI site's mucosal structure and the neoplastic follicles' size. Due to its characteristic structure, very small classic FLs might be detectable mainly in the small intestine.

FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features.

FUS-ERG gene fusion has not been reported in cases of myeloid sarcoma (MS), a subtype of acute myeloid leukemia involving extramedullary anatomic sites. Here, we report a case of a 48-year-old man with primary isolated MS of the anterior mediastinum, who later developed multiple extramedullary recurrences without bone marrow infiltration throughout the course. G-banding analysis of the cells in pericardial effusion at recurrence showed complex karyotypic abnormalities including t(16;21)(p11.2;q22). FUS break-apart fluorescent in situ hybridization analysis showed split signals in biopsy sections at initial diagnosis and recurrence. Reverse transcriptase polymerase chain reaction and direct sequencing demonstrated the presence of the FUS-ERG chimeric gene transcript. The patient underwent cord blood transplantation, but died of pneumonia on day 64. To our knowledge, this is the first report of isolated MS carrying FUS-ERG gene fusion. In future study, relationship between the fusion gene and uncommon clinical features should be investigated in isolated MS.

Characteristics and outcomes of patients diagnosed with norovirus gastroenteritis after allogeneic hematopoietic stem cell transplantation based on immunochromatography.

Norovirus gastroenteritis (NV-GE) is a highly transmittable disease that can lead to fatal outcomes in vulnerable populations including patients after hematopoietic stem cell transplantation (HSCT). Prompt detection of NV is therefore important for HSCT recipients. Immunochromatography (IC) can be used to easily and rapidly diagnose NV-GE by detecting NV antigens. In this study, we examined 642 stool specimens in patients who developed diarrhea after allogeneic HSCT between January 2007 and June 2011. NV was detected in 10 of 350 (2.9 %) HSCT recipients. The median onset of symptoms was 36 days (range 3-93) after HSCT. The median duration of symptoms was 42 days (3-135). A second or subsequent allogeneic HSCT was associated with a higher incidence of NV-GE (P = 0.034). Of four patients who underwent colonoscopy, two showed intestinal graft-versus-host disease (GVHD) histopathology, whereas the other two showed no evidence of GVHD, and thus no need for intensified immunosuppression. None of the patients died of NV-GE. In conclusion, IC may be useful in the differential diagnosis of diarrhea after allogeneic HSCT, and could enable the appropriate adjustment of immunosuppressive drugs and prompt preventive measures.

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis.

Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two proto-oncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P=0.67), whereas HMGA2 expression was associated with decreased overall survival (P=0.05). Quantitative real-time reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells.

SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis.

Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.

Clinicopathological prognostic indicators in 107 patients with diffuse large B-cell lymphoma transformed from follicular lymphoma.

Follicular lymphoma (FL) frequently transforms into diffuse large B-cell lymphoma (DLBCL). To clarify the associated clinicopathological prognostic parameters, we examined the correlation of 11 histopathological parameters with progression-free survival (PFS) and overall survival (OS) in 107 consecutive patients who had DLBCL with pre-existing (asynchronous) or synchronous FL. The patients comprised 58 men and 49 women with a median age of 56 years. For DLBCL, the complete response rate was 81%, overall response rate was 88%, and 5-year PFS and OS rates were 55% and 79%, respectively. Immunohistochemical analysis of the DLBCL component revealed the following positivity rates: CD10, 64%; Bcl-2, 83%; Bcl-6, 88%; MUM1, 42%; GCB, 82%; cMyc index ≥80%, 17%; and Ki-67 index ≥90%, 19%. IGH/BCL2 fusion was positive in 57% of DLBCL cases. In univariate analyses, asynchronous FL and DLBCL (24%, P = 0.021), 100% proportion of DLBCL (29%, P = 0.004), Bcl-2 positivity (P = 0.04), and high Ki-67 index (P = 0.003) were significantly correlated with shorter PFS. Asynchronous FL and DLBCL (P = 0.003), 100% proportion of DLBCL (P = 0.001), and high Ki-67 index (P = 0.004) were significantly correlated with shorter OS. In a multivariate analysis, asynchronous FL and DLBCL (P = 0.035) and 100% proportion of DLBCL (P = 0.016) were significantly correlated with shorter OS. Thus, asynchronism and 100% proportion of DLBCL, that is, FL relapsed as pure DLBCL, or FL and DLBCL at different sites, were significant predictors of unfavorable outcome of patients with DLBCL transformed from FL.

Follow-up data of 10 patients with B-cell non-Hodgkin lymphoma with a CD20-negative phenotypic change after rituximab-containing therapy.

Recently, a CD20-negative phenotypic change in CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) after rituximab therapy was described. We report the follow-up data of 10 B-NHL patients showing this change after rituximab therapy. Ten patients (4 men and 6 women; median age, 57 y) with B-NHL who were initially CD20 positive and became CD20 negative after rituximab therapy were analyzed. Clinicopathologic features, including clinical course, CD20 expression, and histopathology, were examined. CD20 expression in lymphoma cells was evaluated using immunohistochemistry and/or flow cytometry. Histopathologically, diagnosis at initial presentation was follicular lymphoma (FL) in 7 patients; diffuse large B-cell lymphoma in 1; and chronic lymphocytic leukemia in 2. Six patients (60%, 3 FL, 1 diffuse large B-cell lymphoma, and 2 chronic lymphocytic leukemia patients) showed continuous CD20 negativity until 24 months after the phenotypic change. Three patients (30%) with FL regained CD20 expression within 1 to 7 months after detection of the CD20 change. Two patients (20%) with FL, including 1 who regained CD20 expression, showed heterogenous CD20 expression with a CD20-negative low-grade component and a CD20-positive large cell component. The overall response rate to therapy before the CD20-negative change was 70%. We reported the follow-up data of 10 B-NHL patients with a CD20-negative phenotypic change associated with rituximab-containing therapy. The most common histologic phenotypes were continuous CD20 negativity, recovery of CD20 expression within 7 months, and heterogenous CD20 expression. As the changes in morphology and CD20 expression after rituximab therapy vary widely, careful follow-up and rebiopsy are recommended.

Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas.

Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4% of samples and was more prevalent in SCC (69.3%) than in ADC (25.1%), large cell carcinoma (33.3%), and sarcomatoid carcinoma (12.2%) (P < .001). Among ADCs, most mucinous ADCs (75%) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (γ = 0.762, P < .001). IGF-1R-positive tumors were more common in smokers (P = .004), and these tumors were larger (P = .006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches.

Cathepsin D as a potential prognostic marker for lung adenocarcinoma.

We previously identified cathepsin D as a possible marker for lung adenocarcinoma (AD). The purpose of the present study is to evaluate the correlation between cathepsin D expression and clinicopathological findings or prognosis. We conducted immunohistochemistry (IHC) to assess 150 AD tissues. For these 150 tumors, TTF-1 expression, EGFR and KRAS gene mutations, and ALK rearrangements had already been examined. Cathepsin D expression was detected in 44% (66 of 150, IHC score ≥1+) and 27.3% (41 of 150, IHC score ≥2+). Cathepsin D-positive (IHC score ≥2+) tumors were more poorly differentiated than cathepsin D-negative ones, while all lepidic predominant invasive adenocarcinomas showed no cathepsin D expression. Univariate analysis revealed a poor prognosis for cathepsin D-positive lung AD patients with an IHC score ≥2+ (P=0.044). Cathepsin D expression was more frequent in TTF-1-negative than in TTF-1-positive ADs (P=0.034), and more frequent in ADs with EGFR wild genotype than mutant EGFR (P<0.001). Regarding AD patients with ALK rearrangements, 4 were positive for Cathepsin D, while 2 were negative. Cathepsin D expression is indicated to be a possible prognostic marker for lung AD and to correlate with a more poorly differentiated form.

Bulky disease has an impact on outcomes in primary diffuse large B-cell lymphoma of the breast: a retrospective analysis at a single institution.

OBJECTIVES: Primary breast lymphoma (PBL) is rare, and its clinical behavior and standard initial treatment are not yet established. METHODS: We retrospectively analyzed the clinicopathological features and treatment outcomes of 14 patients with primary breast diffuse large B-cell lymphoma. RESULTS: There were nine patients with stage IE and five with stage IIE disease. The median largest tumor diameter was 4.5 cm, and five patients had bulky disease >5 cm. The complete response rate was 94%. However, the 5-year progression-free survival rate was 52% with a median follow-up of 5.2 years. Patients with bulky disease had an unfavorable prognosis. All five patients with bulky disease progressed or relapsed. Of the four patients that recurred in the central nervous system (CNS), three had bulky disease although some received rituximab. There were no CNS recurrences in the three patients who received CNS prophylaxis. All eight patients who responded to radiotherapy (RT) did not have recurrences in the ipsilateral breast, although one patient with bulky disease relapsed in the adjacent regional lymph nodes within the RT field despite immunochemotherapy. CONCLUSIONS: Patients with bulky disease had a poorer prognosis and recurred frequently in the CNS. CNS prophylaxis might yield better outcomes, but a larger, prospective trial is needed to elucidate the optimal initial treatment of PBL in the rituximab era.

Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung.

INTRODUCTION: Recent clinical trials revealed that accurate histologic typing of non-small cell lung cancer, especially squamous cell carcinoma (SCC), is essential. PATIENTS AND METHODS: We analyzed 10 antibodies expression in 150 SCC cases (53 well-, 51 moderately, and 46 poorly differentiated cases) and 159 adenocarcinoma (AC) cases (49 well-, 52 moderately, and 58 poorly differentiated cases). RESULTS: In all SCC and AC cases, p63 was the most sensitive marker for SCC (98.7%), followed by high-molecular-weight (HM) cytokeratin (CK) (97.3%), CK5/6 (93.3%), Sox2 (80%), thrombomodulin (79.3%), desmocollin-3 (72.7%), S100A7 (70.7%), S100A2 (63.3%), and glypican-3 (46.7%). Desmocollin-3 was the most specific marker for SCC (100%), followed by CK5/6 (98%), Sox2 (95.5%), glypican-3 (92.4%), S100A7 (86.8%), thrombomodulin (79.9%), S100A2 (64.6%), p63 (51.6%), and HMCK (33.3%). Thyroid transcription factor-1 (TTF-1) expression was observed in 87.4% of AC cases and 2.0% of SCC cases. When analyzing only poorly differentiated tumors, HMCK was the most sensitive marker for SCC (100%), followed by p63 (97.8%), CK5/6 (87.0%), Sox2 (71.7%), thrombomodulin (58.7%), desmocollin-3 (52.2%), S100A2 (50%), glypican-3 (45.7%), and S100A7 (45.7%). Desmocollin-3 was the most specific marker for poorly differentiated SCC (100%), followed by CK5/6 (98.3%), glypican-3 (94.8%), Sox2 (94.8%), S100A2 (81%), S100A7 (75.9%), thrombomodulin (72.4%), p63 (48.3%), and HMCK (36.8%). The 10-fold crossvalidated classification and regression tree analysis revealed that the combination of CK5/6 and TTF-1 was the best immunohistochemical marker panel for the differentiation between SCC and AC. CONCLUSION: CK5/6 is the best marker for differentiating SCC and AC, irrespective of the histological grade of the tumor. Thus, the combination of CK5/6 and TTF-1 is the most recommended combination of immunohistochemical markers.

Prognostic value of immunohistochemical profile and response to high-dose methotrexate therapy in primary CNS lymphoma.

Several biomarkers have been identified as prognostic factors in primary central nervous system lymphoma (PCNSL). However, the correlation between the histogenetic origin of PCNSL and the response to therapy is still unclear. To elucidate the utility of immunophenotypic markers in predicting clinical outcomes, we investigated 27 immunocompetent patients with PCNSL treated with high-dose methotrexate therapy. Of the 27 patients, 25 received whole-brain radiotherapy after high-dose methotrexate. Immunostaining for CD5, CD10, BCL-6, and MUM-1 was used to determine the immunophenotypic profile of diffuse large B-cell lymphoma of PCNSL. We then evaluated whether immunophenotypic markers were associated with the response to therapy or patients' survival. The response to induction high-dose methotrexate therapy was determined by magnetic resonance imaging after three courses of i.v. high-dose methotrexate. We categorized B-cell lymphomas into three known subtypes: germinal center B-cell (GCB), activated-GCB, and post-GCB subtypes according to immunohistochemical profile. All the BCL-6-positive samples were co-positive for MUM-1 and therefore classified into activated-GCB subtype. BCL-6 expression in this study was associated with poor progression-free survival (P = 0.038). No immunophenotypic markers or subtypes had a significant effect on the response to high-dose methotrexate therapy. However, the response itself was a significant predictor for both progression-free survival (P < 0.001) and overall survival (P = 0.003). Further investigation is needed to assess BCL-6 as a potential prognostic factor in PCNSL.

Minute pulmonary meningothelial-like nodules: clinicopathologic analysis of 121 patients.

Minute pulmonary meningothelial-like nodules (MPMNs) are generally detected incidentally in resected lung specimens. With the development of diagnostic radiology, MPMNs have occasionally been detected on thin-section computed tomography. Their clinicopathologic background remains unclear because there have been no reports of a large series of patients with them. Among 1724 pulmonary resections during a 4 1/2 year period, 271 MPMNs were identified in 121 patients (7.0%) after pathologic examination. Minute pulmonary meningothelial-like nodules were seen more often in females than in males (10.7% versus 4.5%; odds ratio, 2.01; 95% confidence interval, 1.36-2.97; P < .001). Minute pulmonary meningothelial-like nodules were present in all lobes, and the frequency of incidence was not different between lobes. The incidence frequency of MPMNs was not different between age groups. Minute pulmonary meningothelial-like nodules were found more often in patients with malignant pulmonary tumors than in those with benign disease (7.3% versus 2.5%; P = .044). In particular, MPMNs were found more often in patients with lung adenocarcinoma than with other primary pulmonary malignant tumors (9.4% versus 4.5%; odds ratio, 2.33; 95% confidence interval, 1.35-4.02; P < .01). There was no significant difference in clinicopathologic factors between patients with single and multiple MPMNs, except for the size of each nodule.

Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity.

The immunohistochemical expression of thyroid transcription factor-1 (TTF-1) was investigated in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity. Three groups were categorized according to cytological subtype: group A, adenocarcinomas with either a Clara cell and/or type II epithelial cell component (Clara/type II) or a mixed Clara/type II and bronchial surface epithelial cell component (BSE) (mCB), in addition to other components; group B, adenocarcinomas with components including either BSE, a goblet cell component (GOB) or a mixed BSE and GOB component (mBG), and lacking Clara/type II or mCB; group C, adenocarcinomas with only a poorly differentiated component (POR). In group A all Clara/type II, mCB, BSE and the majority of POR were TTF-1 positive. In group B the majority of BSE, POR and all GOB were TTF-1 negative. BSE and POR in both groups had a different phenotype, possibly reflecting their different natural history. In group C 80% of cases were TTF-1 positive, suggesting that the majority were derived from group A tumors.

Cytopathologic factors can predict invasion in small-sized peripheral lung adenocarcinoma with a bronchioloalveolar carcinoma component.

BACKGROUND: Patients with noninvasive, small-sized primary adenocarcinomas of the lung have excellent prognosis after lobectomy. Several researchers have suggested that limited resection could be an acceptable alternative for these patients. Therefore, a preoperative or intraoperative judgment of invasiveness would be one of the critical determinants of the surgical procedure in each case. Cytopathologic findings that can distinguish invasive from noninvasive adenocarcinomas remain to be elucidated. METHODS: Imprint smears were obtained from 60 resected adenocarcinomas with nonmucinous bronchioloalveolar features. Thirteen cytologic factors were evaluated: the presence of necrosis, fibrovascular tissue, proportion of macrophages, the presence of large tumor cell clusters, nuclear grooves, nuclear overlapping, variation in nuclear size, chromatin pattern, presence of a nucleolus, intranuclear inclusions, multinucleated cells, spindle cells, and mitosis. Each factor was examined by univariate analysis for correlation with the presence of histopathologic invasion. RESULTS: In the univariate analysis, 5 cytologic factors--presence of tumor cell clusters consisting of more than 50 tumor cells (P < .001), nuclear overlapping in more than 3 layers (P < .001), presence of nuclear grooves (P = .007), more than 3-fold variation in nuclear size (P < .001), and 1 mitotic cell per 1000 tumor cells (P = .035)--were associated significantly with invasion. Among these, nuclear overlapping in more than 3 layers (P = .003) and more than 3-fold variation in nuclear size (P = .005) were found to be independent predictive factors for invasion by multivariate analysis. CONCLUSIONS: Using imprint smears, the presence of invasion in small-sized primary adenocarcinomas of the lung is predictable by the 2 above-mentioned cytologic findings. Imprint smear cytology may effectively aid intraoperative judgement of invasion in cases where frozen section histology is difficult to interpret.

Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis.

The pathologic features of invasion such as stromal disruption and pleural/vascular involvement have been shown to be of prognostic value in adenocarcinoma. However, the relationship between the degree of invasion, histologic subtype of adenocarcinoma, and prognosis remains unclear. We retrospectively studied 380 peripheral adenocarcinomas of < or = 2.0 cm in diameter with regard to histology and clinical profiles. Their degree of invasive growth was classified into four grades as follows according to the structural deformity and its location in the adenocarcinoma lesion: Grade 0 had a pure bronchioloalveolar growth pattern and no evidence of stromal invasion. Grade 1 had stromal invasion in the area of bronchioloalveolar growth. Grade 2 had stromal invasion localized on the periphery of a fibrotic focus. Grade 3 had stromal invasion into the center of a fibrotic focus. The clinicopathological data were obtained from medical records. The distribution of the histologic grade of invasion was as follows: grade 0 in 85 tumors (22%), grade 1 in 37 (10%), grade 2 in 46 (12%), and grade 3 in 212 (56%). This histologic grade of invasion was closely related to other indicators of tumor spread. Vascular/lymphatic permeation was seen in none of grade 0, in 1 lesion each of grade 1 and grade 2, and 144 (68%) of grade 3. Lymph node metastasis was seen in 57 (27%) lesions of grade 3 but not in grades 0, 1, or 2. The 5-year disease-free survival rates were 100%, 100%, 100%, and 59.6% for tumors with grade 0, grade 1, grade 2, and grade 3 invasion, respectively. Tumors with grade 1 and grade 2 invasion, like tumors with grade 0 invasion (bronchioloalveolar carcinoma), showed an excellent prognosis. Therefore, tumors with grade 1 and grade 2 invasion could be considered "minimally invasive" or "early" adenocarcinomas.

Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma.

BACKGROUND: Several studies have shown the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade, as well as the prognostic impact on patient survival. METHODS: Modified scar grade was defined as follows: Grade 1, no desmoplasia; Grade 2, sparse desmoplastic reaction; Grade 3, dense desmoplastic reaction with diameter of 10 mm or less; Grade 4, dense desmoplastic reaction with diameter exceeding 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension,