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PubMedDate not supplied

Amyloidosis of the alimentary canal: radiologic-pathologic correlation of CT findings.

BACKGROUND: The purpose of the study was to describe the computed tomographic (CT) findings of the alimentary canal and mesentery in amyloid infiltration of the gastrointestinal (GI) tract and to correlate the CT findings with histologic extent and distribution and with amyloid subtype. METHODS: Abdominal CT scans performed between 1988 and 1997 on patients with pathologically proven amyloidosis of the alimentary canal and mesentery. Histology was graded for extent of mucosal, submucosal, and muscularis propria involvement and for degree of interstitial and vascular distribution. CT findings were correlated with histologic extent, histologic distribution, and amyloid histochemical type. RESULTS: Twenty-three patients were included. Four (17%) had bowel wall thickening, which was associated with a higher submucosal extent and interstitial distribution than in patients with normal bowel by CT. Four (17%) patients had bowel wall dilatation without thickening, which was not associated with statistically significantly different histology than in patients with normal bowel by CT. There was no statistically significant correlation between CT findings and histochemical subtype. Mesenteric soft tissue infiltration was seen in two patients, and mesenteric adenopathy was seen in one patient. CONCLUSIONS: Normal bowel is a common abdominal CT finding in amyloidosis of the alimentary canal. When findings are present, GI wall thickening and/or bowel wall dilatation without wall thickening may be seen. Bowel wall thickening on CT correlates with submucosal extent and interstitial distribution of disease. Soft tissue infiltration and adenopathy are also occasionally seen.

Adult↗

PubMed1999

Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery: the effect of age.

BACKGROUND: Although in recent years there has been a dramatic increase in both the incidence of ductal carcinoma in situ (DCIS) and breast-conserving therapy for patients who have this disease, the optimal treatment for these patients remains controversial. Most data regarding outcomes have come from small, retrospective studies, with little data published from prospective, randomized studies. This study investigates the effects of age, postoperative breast irradiation, and other factors on local relapse free survival after breast-conserving surgery for women with DCIS in a large, single-institution series. METHODS: A review was performed of all patients with DCIS who underwent breast-conserving surgery at Memorial Sloan-Kettering Cancer Center from 1978 through 1990. Of the 171 cases identified, data on follow-up and radiation therapy were available for 157. All available pathology slides (132 of 157) were rereviewed to determine histologic subtype, nuclear grade, presence of necrosis, and microscopic tumor size. Sixty-five patients (41%) received postoperative radiation therapy; selection criteria evolved over the time period. The median follow-up was 74 months. RESULTS: Factors that were significantly (P< or =0.05) associated with a lower recurrence rate were older age, noncomedo subtype, lower nuclear grade, negative margins, and postoperative radiation therapy. The 6-year actuarial recurrence rate was 9.6% for patients who received postoperative radiation therapy and 20.7% for patients who had excision only (P = 0.05). Comparison of patients of ages > or =70, 40-69, and <40 years revealed a significantly lower risk of recurrence with increasing age. Actuarial 6-year local relapse rates were 10.8%, 14.0%, and 47.2%, respectively (P = 0.047). A benefit from radiation therapy was suggested for each age group. There was no statistically significant correlation between age group and any histologic factor examined. In multivariate analysis, only margin status was statistically significant (P = 0.05). CONCLUSIONS: In addition to margin status, pathologic factors, and the use of radiation therapy, age is another factor that should be considered in assessing the risk of local recurrence after breast-conserving surgery for patients with DCIS.

Adult↗

PubMed2005

[Is the microscopic morphology of thymoma of clinical significance?].

UNLABELLED: Thymomas are rare mediastinal tumors that have heterogeneous microscopic morphology and uncertain outcome. AIM: The aim of the study was to evaluate the practical usefulness of WHO classification by correlation of histological subtype of thymoma with staging, symptoms and epidemiology. MATERIAL AND METHODS: 87 cases of thymomas was reclassified according to the WHO Histologic classification and Masaoka staging system. Clinical symptoms, age and sex of the patient were taken into consideration in each case. RESULTS: The histological subtypes was diagnosed in order of frequency: AB (n = 21; 24%), B2 (n = 19; 22%), B1 (n = 14; 16%), A (n = 6; 7%), C (n = 4; 5%), B3 (n = 3; 3%). Combined types was observed in 17 (20%) cases. Tendency to invasion increased as follows: A < AB < B1 < B2 < B3 < C. The median value of patients' age was: type A--67,5 years, type AB--62 yrs., type B1--48 yrs., type B2--52 yrs., type B3--32 yrs. and type C (thymic carcinoma)--49,5 yrs. No correlation was found between histological type and sex of patient. The most often clinical symptom--myasthenia, accompanied predominantly B2 thymomas. CONCLUSIONS: The WHO classification is useful in routine pathologic examination of thymomas, because it enables to distinguish histological subtypes with different clinical representation.

Adult↗

PubMed2004

Excitotoxic and post-ischemic neurodegeneration: Involvement of transglutaminases.

Neurodegeneration induced by excitotoxicity is a common feature in various neurological disorders. This pathological condition is caused by prolonged stimulation of glutamate receptor subtypes, followed by both intracellular Ca2+ overload and activation of specific genes, resulting in synthesis of enzymes involved in cell stress response. Using experimental in vitro models of excitotoxicity, we demonstrated that glutamate exposure up-regulated tissue transglutaminase in primary cultures of both cerebellar granule cells and astrocytes. These changes were consequent to receptor-mediated Ca2+ influx, as demonstrated by the inhibition with selective antagonists, MK-801 and GYKI 52466. Early increases in different transglutaminase isoforms were also observed in global cerebral ischemia, which closely resembles neuronal damage caused by NMDA receptor activation. These findings agree with a postulated role for transglutaminases in molecular mechanisms of several neurodegenerative diseases. Indeed, increased cross-linking reactions could be of pathologic relevance, as part of biochemical changes observed in neurological disorders.

Animals↗

PubMed1998

Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.

Aged↗

PubMed1992

Ovarian pathology.

During the period under review (December 1990 through January 1992), the revised World Health Organization Histological Classification of Ovarian Neoplasms and Tumor-like Lesions was completed, and it is presented herein. This system of classification incorporates recent advances and includes newly recognized entities and subtypes. A number of significant reviews covering the whole field of ovarian tumor pathology have been published, including reviews of clinical syndromes associated with ovarian neoplasia, metastatic tumors of the ovary, and the interrelationships between ovarian and appendiceal mucinous tumors and pseudomyxoma peritonei.

Endocrine System Diseases↗

PubMed2003

Immunopathogenesis of chlamydia trachomatis infections in women.

OBJECTIVE: To develop a model of pathogenesis by which Chlamydia trachomatis progresses from acute to chronic infection, and finally serious disease (salpingitis, tubal occlusion). DESIGN: Review of current literature located through web-based Medline searches using key words: Chlamydia trachomatis, immunology, cytokines, heat shock protein, infertility. RESULT(S): Cell-mediated immune mechanisms appear to be critical in determining whether acute infection is resolved or progresses into chronicity with pathological outcome. What determines the particular immune pathway depends on a range of determinants-HLA subtype and human genetics, cytokine profile, infectious load, route of infection, and endocrinology. A clearer picture of the natural history of chlamydial pathology may assist in providing better predictors of those women who may go on to develop significant sequelae after infection. CONCLUSION(S): Predicting those who may develop serious disease, including infertility, may contribute to improved management of such persons during earlier stages of infection and assist in prevention.

Chaperonin 60↗

PubMed1993

Determining the incidence of different subtypes of stroke: results from the Perth Community Stroke Study, 1989-1990.

OBJECTIVE: To determine the incidence and case fatality of seven distinct subtypes of stroke in Perth, Western Australia. DESIGN AND SETTING: A population-based descriptive epidemiological study. SUBJECTS: All residents of a geographically defined segment of the Perth metropolitan area (estimated population 138,708 persons) who had a stroke or transient ischaemic attack between 20 February 1989 and 19 August 1990, inclusive. MAIN OUTCOME MEASURES: The following subtypes of stroke were classified according to standard clinical, radiological and pathological criteria: types of cerebral infarction, namely, large artery (thrombotic) occlusive infarction (LAOI), cerebral embolic infarction (EMBI), lacunar infarction (LACI) and boundary zone infarction (BZI); primary intracerebral haemorrhage (PICH); subarachnoid haemorrhage (SAH); and stroke of undetermined cause. RESULTS: Over the 18-month study period 536 stroke events were registered, of which 86% (95% confidence interval, 83%-89%) had a defined "pathological" diagnosis on the basis of computed tomographic scanning, magnetic resonance imaging or necropsy. Cerebral infarction accounted for 71% of cases (95% CI, 68%-75%), PICH 11% (95% CI, 9%-14%) and SAH 4% (95% CI, 2%-5%). The 382 cases of cerebral infarction included LAOI (in approximately 71%), EMBI (15%), LACI (10%) and BZI (5%). While the incidence of all subtypes of stroke increased with age, there were age and sex differences in their proportional frequency, management and prognosis: patients with PICH, SAH and EMBI were more likely to be admitted to hospital, and these conditions carried the highest early case fatality. Over all, the 28-day case fatality was 24% (95% CI, 20%-28%), but varied from 0 for LACI and BZI, to 37% (95% CI, 15%-59%) for SAH and 35% (CI, 23%-47%) for PICH. CONCLUSIONS: In this study, we found considerable differences in incidence rates, the effect of age and sex on incidence rates, and prognosis for the different subtypes of stroke. Hospital-based studies are likely to be selectively biased by emphasising strokes that are severe and require admission to hospital. These data have important implications in the design and evaluation of clinical trials of therapy for stroke.

Adult↗

PubMed1989

The subtypes, distribution and location of human papillomavirus DNA in genital warts and genital Bowen's disease--a study using in situ DNA.DNA hybridization.

The aim of this study is to investigate the difference in subtypes and distribution of human papillomavirus (HPV) between the benign pathological condition- Genital wart (condyloma acuminatum, verruca- like lesion and papular lesion) and genital Bowen's disease (Bowenoid papulosis, Mollucum contagiosum with Bowenoid papulosis and Condyloma acuminatum with verruca- like lesion and pathological bowenoid change) of genitalia by in situ DNA.DNA hybridization. In situ DNA.DNA hybridization was performed by hybridizing the RNAse treated and denatured frozen skin section with 3H-labeled HPV 6, 11, 16 and 18-DNAs probes and then developed autoradiogram on a glass slide. The results reveal that: (1) The benign cases are strongly associated with HPV 6/11, while the bowenoid cases are associated with HPV 16/18, indicating 16 positive in 24 cases and 3 positive in 5 cases respectively; (2) Four of sixteen benign cases were doubly infected with HPV 6/11 and 16/18; and 2 of 2 bowenoid cases were infected with HPV 16/18 only (3) In benign cases, HPV distributes through the upper third of epidermis and in bowenoid cases, HPV scatters throughout the whole epidermis including parabasal layers. These findings may indicate that the subtypes of HPV, the interaction of weak oncogenic virus (HPV 6/11) and strong oncogenic virus (HPV 16/18) and the presence of HPV on proliferating cells (parabasal layers) all play a part in oncogenicity. The detectability of HPV 6/11 DNA in both the nucleus and cytoplasm indicate that: 1). In situ DNA.DNA hybridization is a more sensitive method than the immunological detection of capsid antigen. 2). In addition to the nucleus, the cytoplasm is a site through which HPV 6/11 virus should pass during their life cycle. Using PEG hybridization mixture, it was revealed that 6 of the 6 HPV 6/11 positive condyloma acuminata harbored HPV 6. This result indicates that the subtype of HPV determine the gross morphology of skin lesion.

Bowen's Disease↗

PubMed2003

Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy. METHODS: The medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid-stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival. RESULTS: The median follow-up was 3.2 years (range, 0.2-9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high-risk group had 1% survival at 1 year and no survivors at 3 years. CONCLUSIONS: In patients with metastatic RCC who were treated with nephrectomy and IL-2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials.

Adult↗

PubMed2005

Gene expression profiling identifies molecular subtypes of inflammatory breast cancer.

Breast cancer is a heterogeneous disease. Comprehensive gene expression profiles obtained using DNA microarrays have revealed previously indistinguishable subtypes of noninflammatory breast cancer (NIBC) related to different features of mammary epithelial biology and significantly associated with survival. Inflammatory breast cancer (IBC) is a rare, particular, and aggressive form of disease. Here we have investigated whether the five molecular subtypes described for NIBC (luminal A and B, basal, ERBB2 overexpressing, and normal breast-like) were also present in IBC. We monitored the RNA expression of approximately 8,000 genes in 83 breast tissue samples including 37 IBC, 44 NIBC, and 2 normal breast samples. Hierarchical clustering identified the five subtypes of breast cancer in both NIBC and IBC samples. These subtypes were highly similar to those defined in previous studies and associated with similar histoclinical features. The robustness of this classification was confirmed by the use of both alternative gene set and analysis method, and the results were corroborated at the protein level. Furthermore, we show that the differences in gene expression between NIBC and IBC and between IBC with and without pathologic complete response that we have recently reported persist in each subtype. Our results show that the expression signatures defining molecular subtypes of NIBC are also present in IBC. Obtained using different patient series and different microarray platforms, they reinforce confidence in the expression-based molecular taxonomy but also give evidence for its universality in breast cancer, independently of a specific clinical form.

Adenocarcinoma↗

PubMed2004

[Psychodermatology: current state of the problem].

An analysis of comorbidity of psychiatric and dermatological pathology in historical, epidemiological and clinical aspects is presented. Psychocutaneous disorders (delusional parasitosis, hypochondria circumscripta, obsessive-compulsive disorders with self-mutilations, pathomimia) play a central role in systematics elaborated in the present study. The authors suggest that delusional parasitosis is a subtype of paranoiac psychosis (paranoia, paranoiac schizophrenia). Psychiatric disorders triggered by dermatological pathology were specified as nosogenous reactions, depressive reactions with sociophobia, pathologic personality development (paranoiac, sensitive, hypochondriac). Atopic dermatitis, eczema, urticaria, psoriasis, herpes simplex, alopecia areata, rosacea, etc, are regarded among dermatological psychosomatic disorders with psychogenic manifestation/exacerbation.

Comorbidity↗

PubMed2001

[Renal cell carcinoma metastatic to the ovary: a case report].

A 47-year-old woman underwent left radical nephrectomy in 1995, and pathological diagnosis showed a primary renal cell carcinoma with clear cell subtype. Four years later on her routine checkup, abdominal computerized tomography revealed a 9-cm of predominantly solid and partially cystic tumor in the pelvic cavity. The patient was referred to Gynecologic Department and a total hysterectomy with bilateral salpingo-oophorectomy was subsequently performed under the diagnosis of a left ovarian tumor. A cut surface of the solid component of the tumor was macroscopically yellowish. Pathological examination revealed alveolar growth of tumor cells with abundant clear cytoplasm including fat components. In some areas of the tumor, there were patterns of tubular structures which were cystically dilated. The typical findings usually found in the primary ovarian clear cell adenocarcinoma were absent in the tumor, and the final pathological diagnosis was left ovarian metastasis of renal cell carcinoma. The ovarian metastasis of renal cell carcinoma is quite rare and to our knowledge only eleven cases were reported in the past 20 years. We report on a case and review the literature.

Carcinoma, Renal Cell↗

PubMed2000

Elevated cortical extracellular fluid glutamate in transgenic mice expressing human mutant (G93A) Cu/Zn superoxide dismutase.

Transgenic mice expressing a mutated (G93A) human Cu/Zn superoxide dismutase (SOD1) develop motor neuron pathology and clinical symptoms similar to those seen in patients with amyotrophic lateral sclerosis. Loss of motor neurons is most prominent in lumbar, followed by cervical cord and then brainstem. No significant cell death has been reported in motor cortex. The integrity of the cortical glutamate reuptake systems was evaluated using intracerebral microdialysis and western immunoblot assays for the glutamate transporters GLT-1, GLAST, and EAAC1. The basal extracellular fluid levels of aspartate, glutamate, glutamine, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid were evaluated by HPLC. The extraction fraction of L-3H]glutamate, corrected with [14C]mannitol, was also evaluated. GLT-1, EAAC1, and GLAST protein levels were determined by semiquantitative chemiluminescence immunoblot of proteins from membrane-enriched fractions. The relative optical density of film was translated into relative protein level by comparison with a standard control mouse. The SOD1 mutant mice demonstrated a significant (p < 0.05) increase in basal levels of extracellular aspartate and glutamate. In addition, when the glutamate extraction fraction was challenged with exogenous unlabeled glutamate (500 microM) by reversed microdialysis, the glutamate extraction fraction in the mutant SOD1 mice was decreased significantly from control levels. The SOD1 mutant mice demonstrated no difference in the cortical protein levels of the glutamate transporter subtypes. This study demonstrates that in areas of no visible pathology and no loss of glutamate transporter proteins, SOD1 mutant mice have elevated extracellular fluid aspartate and glutamate levels and a decreased capacity to clear glutamate from the extracellular space.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

Cortical glucose metabolism is altered in aged transgenic Tg2576 mice that demonstrate Alzheimer plaque pathology.

Alzheimer's disease is associated with markedly impaired cerebral glucose metabolism as detected by reduced cortical desoxyglucose utilization, by altered activities of key glycolytic enzymes or by reduced densities of cortical glucose transporter subtypes. To determine whether formation and/or deposition of beta-amyloid plays a role in the pathology of glucose metabolism, transgenic Tg2576 mice that overexpress the Swedish mutation of the human amyloid precursor protein and demonstrate a progressive, age-related cortical and hippocampal deposition of beta-amyloid plaques, were used to study expression and activity of key enzymes of brain glycolysis (phosphofructokinase, PFK) and glyconeogenesis (fructose1,6-bisphosphatase; FbPase). Quantitative RT-PCR revealed high expression levels of both C- and M-type PFK mRNA in non-transgenic mouse cerebral cortex, whilst there was little expression of the L-type. In 24-month-old transgenic Tg2576 mouse cortex, but not in 7-, 13-, and 17-month-old mice, the copy number of PFK-C mRNA was significantly reduced in comparison to non-transgenic littermates, while the mRNA level of the other PFK isoforms and FbPase did not differ between transgenic and non-transgenic tissue samples. In situ hybridization in brain sections from aged Tg2576 mice revealed reduced PFK-C mRNA expression in beta-amyloid plaque-associated neurons and upregulation in reactive astrocytes surrounding beta-amyloid deposits. The decreased PFK-C protein level detected by Western analysis in cerebral cortical tissue from 24-month-old transgenic Tg2576 mice was accompanied by reduced enzyme activity of PFK in comparison to non-transgenic littermates. Our data demonstrate that impairment of cerebral cortical glucose metabolism occurs only due to the long-lasting high beta-amyloid burden. This results from a reduction in glycolytic activity in beta-amyloid plaque-associated neurons and a concomitant upregulation in reactive, plaque-surrounding astrocytes.

Age Factors↗

PubMed2006

Pathologic findings of lung tumors diagnosed on baseline CT screening.

Sixty-five people had a resection of their baseline screen-diagnosed lung cancers in the Early Lung Cancer Action Program. Forty-nine of the carcinomas were solitary, and 42 of these were adenocarcinomas. More than 1 carcinoma was found in 16 patients after pathologic examination of the lobectomy specimen; 15 of the 16 second carcinomas were adenocarcinomas, mixed subtype. Eighteen cases were submitted by local pathologists as Bronchioloalveolar carcinomas but were found to be invasive adenocarcinomas according to the World Health Organization classification by the Pathology Review Panel. Of the 65 resected cases, 57 were N0, 7 were N1, and 1 was N2. Upon careful review of the lobectomy specimens, 49 cases had solitary malignancies, 30 were Stage IA, 13 Stage IB, 3 Stage IIA, 2 Stage IIB, and 1 Stage IIIA on the basis of the American Joint Committee on Cancer/International Union for Cancer Control criteria. In the 16 cases found to have multiple malignancies, 6 had histologically different carcinomas and the remaining 10 had histologically identical malignancies. Eighty-three percent (76/92) of the carcinomas invaded the stroma with destruction of normal lung, and 21% (19/92) also showed either pleural or angiolymphatic invasion, even though 88% (57/65) of the carcinomas were free of lymph node metastases. This report describes the pathologic findings of the resected cases. Histopathologic distinctions among atypical adenomatous hyperplasia, bronchioloalveolar carcinomas, and invasive adenocarcinoma are described in detail.

Aged↗

PubMed2026

Topologically distinct intratumoral heterogeneity scores for predicting high-risk pathological grades in invasive lung adenocarcinoma: A multicenter study across four institutions.

High-risk subtypes of invasive lung adenocarcinoma (IAC), particularly micropapillary- or solid-predominant patterns, are closely associated with poor prognosis. This multicenter retrospective study developed and validated a predictive model for the preoperative identification of these high-risk subtypes using topologically distinct intratumoral heterogeneity (ITH) scores derived from CT images. The study included 1,051 patients with IAC. Two complementary ITH scores were developed: a two-dimensional ITH score, which integrated local radiomics features with global pixel distribution patterns on the largest cross-sectional CT slice, and a three-dimensional ITH score, which extended this quantification across the entire tumor volume. Clinicoradiological features and ITH scores were incorporated as model inputs to construct six base machine learning classifiers and a final stacking ensemble classifier. Model interpretability and robustness were evaluated using SHapley Additive exPlanations (SHAP)-based ablation analyses. An independent dataset from The Cancer Imaging Archive (TCIA) was used for external validation to investigate associations between ITH scores and pathological characteristics, genomic features, recurrence-free survival, and overall survival. The stacking ensemble classifier achieved the best predictive performance, with an area under the receiver operating characteristic curve of 0.875, outperforming models based solely on radiomics features (0.834) or clinicoradiological features (0.792). SHAP analysis identified the 3D ITH score as the most influential contributor to model output, and TCIA validation showed that higher 3D ITH scores were associated with more aggressive tumor biology and poorer survival outcomes. The topologically distinct 3D ITH score may provide a clinically meaningful imaging biomarker for preoperative risk stratification in IAC.

Journal Article↗

PubMed1986

Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience.

Histopathologic peer review of specimens from 216 consecutive patients with soft-tissue or bone sarcomas on Southeastern Cancer Study Group protocols was performed by a panel of three pathologists. Subtype of sarcoma, degree of confidence in diagnosis, and grade were compared with agreement or disagreement in pathologic opinion from the primary member institution v the pathology review panel. The most common soft-tissue sarcoma was leiomyosarcoma, followed by malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, malignant schwannoma, and rhabdomyosarcoma. There was total agreement between the primary pathologist and reviewer in 66% of cases. However, 12 cases (6%) were considered on review to not be sarcomas. In 27% of cases the subtype of sarcoma was felt to be incorrect by reviewers. Discordant diagnoses were more common when the confidence of the pathologist was less and when the tumor was of higher grade. There was no improvement in frequency of agreement in the second half of the study, despite educational workshops. We conclude that histologic peer review is important in sarcoma studies and is essential in many patients with presumed sarcomas.

Bone Neoplasms↗