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Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: a meta-analysis of diagnostic test characteristics.

The current goal of interferon treatment for chronic hepatitis C is to normalize alanine aminotransferase (ALT) and to eradicate detectable viral RNA. Many patients do not achieve this objective during treatment, and most do not sustain these outcomes after interferon is discontinued. However, biochemical or virological responses to interferon may not reflect accurately the histological consequences of therapy. The aim of this study was to determine the extent to which the biochemical measures reflect the histological outcomes in the treatment of hepatitis C with interferon alfa using a meta-analysis of diagnostic test characteristics. The data sources were English and non-English language studies retrieved from Medline (from 1966 to December 1995). The study selection included studies in which interferon alfa was used for treatment of chronic hepatitis C with liver biopsies performed before and after therapy. Data on histological and biochemical outcomes were extracted independently by two reviewers. Two separate criteria were used for defining histological response. When strict definitions of histological improvement were considered, histology improved in 28% (95% confidence interval [95% CI], 17%-43%) of patients after interferon treatment. The sensitivity and specificity of the ALT for determining histological change were 70% (95% CI, 56%-81%) and 66% (95% CI, 56%-75%), respectively. As many as 17% (95% CI, 9%-30%) of subjects with an abnormal ALT at the end of therapy may have improved histologically after interferon therapy. When less stringent definitions of histological improvement were considered, 62% (95% CI, 51%-72%) improved after therapy. The sensitivity and specificity of the ALT for determining histological change were 55% (95% CI, 44%-65%) and 75% (95% CI, 67%-81%), respectively. As many as 51% (95% CI, 38%-64%) may have improved, despite failure to normalize ALT. A substantial number of patients may improve histologically after interferon therapy. The significance of histological changes observed after interferon therapy must be weighed against the limitations of liver biopsy and the uncertain natural history of hepatitis C. Nevertheless, the ALT does not always reflect liver histology accurately after interferon alfa treatment and may underestimate histological improvement.

Alanine Transaminase↗

Concurrent skin and nerve histology in leprosy and its role in the classification of leprosy.

Concurrent skin and nerve histology was evaluated in 60 leprosy patients (25 BT, 28 BL and 7 LL). The twin aims were to study the comparative histology and the usefulness of nerve histology in the classification of the disease. In BT patients, clinical and histological classification was in agreement in 11 (44%) skin and 17 (68%) nerve biopsies. Concurrent skin and nerve histology was in consonance in 14 (56%) BT patients, while in 6 (24%) patients, only nerve histology was helpful in the classification of the disease, the skin histology being non-specific. Nerve histology was classified as BL in 3 (12%) BT patients, the skin histology was non-specific. In the BL group, the histology of 23 (82.4%) nerve biopsies correlated with the clinical classification, in contrast to skin histology which correlated with clinical assessment in 19 (68%) patients only. In the LL patients, the histology of nerve correlated with the clinical classification in 5 patients (71.4%), compared to histology of the skin in 4 (57%) patients only. The GF was higher in the nerves than in the skin throughout the leprosy spectrum (BT, BL, LL); the difference was, however, marginal in BL leprosy. The average bacteriological index (BI) was higher in nerves (4+) compared to that of skin histology and slit skin smears (3+) in BL leprosy. There was, however, no difference in the BI of the slit skin smears, skin and nerve biopsies in lepromatous leprosy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Clinico-histologic characteristics of spinocellular carcinoma of the skin].

INTRODUCTION: Authors present clinical-histological characteristics of squamous cell carcinomas of the skin in patients treated at the Clinic of Infectious and Dermato-Venereology Diseases in Novi Sad in the period from 1989 to 1995. MATERIAL AND METHODS: The examined group comprised 26 cases (2.32%) with histologically verified squamous cell carcinomas of the skin out of 1119 nonmelanomatous epithelial skin tumors, clinically examined by dermatologists and treated by x-ray surface therapy. All patients with SCC were clinically examined by dermatologists at the Clinic of Dermatology and Venereology in Novi Sad, while histological examinations were performed by pathologists of the department of Pathology and Histology of the Faculty of Medicine in Novi Sad. Tumor biopsy specimens were obtained by shave biopsy, saucer biopsy and punch biopsy. All the biopsy specimens wee histologically examined and verified with standard methods with haematoxyllineosin-staining. RESULTS: In the group of examined patients most were with SCC--that is exophytic tumor of the skin in 16 cases (61.54%). Histological examination revealed: squamous cell carcinoma of the skin in 9 cases (56.25%), keratotic squamous cell carcinoma in 5 cases (31.25%) and invasive squamous cell carcinoma in 2 cases (12.50%). In the examined group there were also 9 cases of SCC (36.41%) with clinical forms of endophytic tumor of the skin. By histological examination the following tumors were diagnosed: Morbus Bowen in 3 cases (incipient squamous cell carcinoma of the skin) (33.33%); squamous cell carcinoma of the skin in 5 cases (55.56%) and keratotic squa- mous cell carcinoma in 1 case (11.11%). In one case SCC with clinical features like keratoacanthoma was found (3.85%), while by histological examination keratotic squamous cell carcinoma of the skin was diagnosed. DISCUSSION: In regard to the biopsy technique, SCC of the skin was diagnosed mostly as spinocellular carcinoma of the skin in 14 cases (53.85%) without a more precise description of the degree of tumor cells degeneration as well as tumor edge characteristics and type of histological type of tumor. Keratotic squamous cell carcinoma was found in 7 cases (26.92%); it is a tumor of mature structure (1-2 Broders' grade of clinical stage of tumors), but also without a detailed description of the tumor edge and type of histological type of tumor. Invasive squamous cell carcinoma was found in 2 cases (7.96%) and it reveals a SCC of the skin with deep infiltration into the dermis and hypodermis, sometimes involving the neighboring tissue (cartilage tissue, bone, muscle tissue and so on). This histological form of SCC had 3-4 Broders' grade of clinical stage of tumors. CONCLUSION: Authors of the paper conclude that histological examinations of SCC of the skin are necessary meaning detailed analysis: degree of differentiation of tumor cells by Broders' examination, examination of tumor edges and histological types of tumor. The incisional biopsy of tumor lesions had only been used to confirm clinical diagnosis in order to perform x-ray therapy, but it could not meet necessary criteria the excisional biopsy could in regard to evaluate tumor edges and histological type of the tumor.

Aged↗

A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi.

BACKGROUND: Nevi that are clinically atypical and histologically dysplastic have been associated with increased melanoma risk. There are few reproducibility studies or population-based studies of nevus histology. OBJECTIVE: Our purpose was to quantify concordance in histologic diagnosis of melanocytic lesions among a diverse group of pathologists, to assess intraobserver concordance by comparing readings of the same slide as well as of adjacent recuts from the same block, to correlate histology with nevus appearance and melanoma risk, and to estimate the range of prevalence of histologic dysplasia. METHODS: Histologic slides were prepared from 149 tissue blocks of pigmented lesions from melanoma cases, relatives, and controls. Six dermatopathologists independently evaluated the lesions for histologic dysplasia, without prior agreement on criteria. RESULTS: According to kappa statistics, intraobserver reproducibility was substantial, and interobserver concordance was fair, despite differences in criteria. The estimated prevalences of histologic dysplasia for the six pathologists ranged from 7% to 32%. Histologic dysplasia was correlated with nevus size for most observers, confounding the observed correlation between nevus appearance and histology. CONCLUSION: Although experienced dermatopathologists use different diagnostic criteria for histologic dysplasia, their usage is consistent. Histologic changes ascribed to melanocytic dysplasia are prevalent in the white population for all pathologists. The term nevus with histologic dysplasia should be used in preference to dysplastic nevus.

Adult↗

Bronchioloalveolar cell carcinoma: impact of histology on dominant CT pattern.

The authors set out to determine how histologic variability in bronchioloalveolar cell carcinoma impacts dominant radiographic patterns shown by computed tomography (CT). Thoracic CT's of all patients with pathologically confirmed bronchioloalveolar cell carcinoma diagnosed over a 36-month period were reviewed without knowledge of underlying histologic type. The dominant CT pattern was recorded as 1) air space consolidation; 2) focal nodule or mass; and 3) multicentric nodules or masses. Nodules and masses were further characterized according to borders, distribution, and associated findings, including spiculations and air bronchograms. Histology was independently reviewed. Twenty-seven patients, 16 women and 11 men, mean age 60 years, were diagnosed with bronchioloalveolar cell carcinoma. In 6 (22%) of the 27 cases, the histology was mucinous, with malignant goblet cells identified. Five (83%) of the six mucinous neoplasms manifested as air space consolidation and three (50%) of the six presented with multiple nodules, in which two had coexisting air space consolidation. Of the remaining 21 cases (78%) with nonmucinous histology, the primary malignant cells of origin included Clara cells (n = 8), tall columnar epithelial cells (n = 7) and alveolar type II pneumocytes (n = 6). Sclerosis was a dominant histologic feature in 14 (67%) of the 21 cases. Seventeen (81%) of the nonmucinous neoplasms presented as isolated nodules or masses and four (19%) presented as multiple nodules or masses. Of these four patients with multifocal disease and nonmucinous histology, multiple bronchioloalveolar adenomas accounted for multicentricity in two of the patients. Significant correlations included air space consolidation with mucinous histology (p = 0.001) and focal nodule or mass with nonmucinous histology (p = 0.001). At CT of bronchioloalveolar cell carcinoma, the patterns of air-space consolidation correlate with mucinous histology and isolated nodules or masses with nonmucinous histology. The pattern of multiple nodules or masses, however, did not correlate with histology. Coexisting bronchioloalveolar adenomas can contribute to apparent multicentric disease in patients with nonmucinous histology.

Adenocarcinoma, Bronchiolo-Alveolar↗

Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both?

The differential diagnosis between Helicobacter pylori (H pylori-associated chronic gastritis and low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) and the assessment of endoscopic biopsy specimens after treatment of lymphoma can be problematic. Although immunocytochemistry can be used to identify clonal B-cell populations, which are characteristic of MALT lymphoma, its application to small biopsy specimens and the subsequent interpretation can be difficult. The polymerase chain reaction (PCR) can detect clonal B-cell populations by analysis of the Ig heavy chain gene in routinely fixed paraffin-embedded material and might provide a useful tool in the assessment of these specimens. We have investigated the value of histology and PCR in the diagnosis of lymphoma and its followup in formalin-fixed paraffin-embedded gastric endoscopy biopsy specimens from 69 sequential patients selected on the basis of a dense mucosal lymphoid infiltrate associated with H pylori infection. Histologic evidence of MALT lymphoma was identified in 13 cases, 9 of which showed PCR-detected monoclonality. In 12 of 13 cases, H pylori was eradicated, and in 11 of 12 cases, histologic regression of the lymphoma followed. PCR evidence of monoclonality disappeared in 6 of 9 originally monoclonal cases. This was synchronous with histologic remission in 1 case, but lagged in the remaining 5 cases by up to 28 months. Two of the 3 of the 9 cases originally monoclonal by PCR that have not shown molecular regression have monoclonal-amplified products 17 and 24 months after negative histology. In 3 cases, the histology of the biopsies was considered indeterminate or discordant. In 1 of these cases, the histologic features were obscured by crush artefact. In a second case, there was molecular evidence of monoclonality in the absence of histologic features suggestive of lymphoma; this persisted after H pylori eradication. An additional single case originally diagnosed as reactive developed a PCR detectable clonal population 29 months after original evaluation in the absence of histologic features of lymphoma but in the presence of persistent H pylori infection. These findings suggest that the histologic assessment of gastric biopsies remains the method of choice for the diagnosis of lymphoma in gastric endoscopic biopsies with a dense mucosal lymphoid infiltrate. PCR provides a useful technique to support the diagnosis if clonal amplification products are found. The significance of PCR detected clonality in the absence of histologic evidence of lymphoma in uncertain but may represent a stage of tumor progression/regression when the clonal population is insufficient to be detected by conventional histology. This is supported by the evidence that PCR-detectable monoclonality can persist after treatment and the disappearance of histologically detectable lymphoma.

Adolescent↗

Histology correlation with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology diagnoses: An argument to ensure ASCUS follow-up that is as aggressive as that for LSIL.

The purpose of the present study was to compare histology outcomes of cytological atypical squamous cells of undetermined significance (ASCUS) to the histology outcomes of cytological low-grade squamous intraepithelial lesion (LSIL). Cases with a cytology diagnosis of ASCUS and LSIL that had correlative histology obtained within 3 mo of the cervico-vaginal smear were accrued from the files of the Cytology and Histology Departments of Mercy Hospital Medical Center (Des Moines, IA). All of the cytology cases were examined by a cytotechnologist, a cytopathologist, and the histopathologist who signed out the biopsy material. The laboratory's benign: ASCUS: LSIL: HSIL + ratio was 94.0%: 3.8%: 1.5%: 0.7% for the time period of this analysis; its ASCUS:SIL proportion was 1.76. Histology correlations to 249 ASCUS cases showed 45 (18%) CIN2s (cervical intraepithelial neoplasm 2) or CIN3s, 134 (54%) CIN1s, and 70 (28%) nonneoplastic biopsies. Ten of 24 (42%) ASCUS cases that showed histological CIN3 and seven of 21 (33%) ASCUS cases that showed histological CIN2 contained atypical immature squamous metaplastic cells, while the remainder showed squamous cells with mature, superficial/intermediate-type cytoplasm. Histology correlations to 576 LSIL cases showed 96 (17%) CIN2s or CIN3s, 397 (69%) CIN1s, and 83 (14%) nonneoplastic biopsies. One hundred forty-six (59%) ASCUS and 424 (74%) LSILs had histological koilocytosis with nuclear atypia (KA); the sole histological finding of KA was seen among 76 (30.5%) ASCUS and 146 (25.3%) LSIL cases. The majority of cytological ASCUS and LSIL cases selected by clinicians for biopsy have histological CIN and a substantial minority show CIN2 and CIN3, which, in the case of ASCUS, is frequently associated with atypical immature squamous metaplastic cells. There is a high prevalence of histological KA among ASCUS and LSIL cases. Diagn. Cytopathol. 21:292-295, 1999.

Cervix Uteri↗

Basal cell carcinoma histological clearance margins: an analysis of 1539 conventionally excised tumours. Wider still and deeper?

An analysis of peripheral and deep margins of histological clearance around 1539 consecutive basal cell carcinomas excised by conventional surgery showed that 81 lesions (5.3%) were incompletely excised peripherally; 36 lesions (2.3%) were incompletely excised deeply; 13 lesions (0.8%) were incompletely excised peripherally and deeply. Nine hundred and ninety-six lesions (65%) were excised with a peripheral histological clearance margin<5mm (0.1-4.9mm), whereas 1303 lesions (85%) were excised with a deep histological clearance margin<5mm (0.1-4.9mm). Four hundred and eight lesions (27%) had a peripheral histological clearance margin of 5.0-9.9mm, whereas 170 lesions (11%) had a deep histological margin of 5.0-9.9mm. Peripheral histological clearance margins exceeded 10mm in 41 lesions (3%) and deep histological margins exceeded 10mm in 17 lesions (1%). Thus 30% of peripheral histological margins were 5mm or more but only 12% of deep histological margins were 5mm or more. Despite a relative sparing of deep tissue, incomplete excision in depth affected only 36 lesions compared with 81 incomplete peripheral excisions. Peripheral histological clearance was <5mm (0.1-4.9mm) for 55% of temple lesions, 50% of scalp lesions and 43% for limb lesions. In the cosmetically sensitive areas of peri-orbital region, nose, cheek, lip, neck and chin more than 70% of lesions were excised with a peripheral histological margin<5mm. This study of conventional surgical excision of basal cell carcinomas with an incomplete excision rate of 8% has shown that 65% of lesions were excised with <5mm histological clearance peripherally and 85% with <5mm deep clearance. These figures for 'normal tissue sacrifice' are not excessive when compared with those of 'tissue sparing' Mohs' micrographic surgery in which the operator may take a margin of several millimetres of normal tissue in the initial 'slice', or in the subsequent 'safety margin' beyond the eventual tumour free plane. However, peripheral margins did exceed 5mm in more than 30% of lesions of scalp, temple and forehead, and for these sites where even with loupe magnification the tumour edge could be difficult to define, either frozen section control or Mohs' technique, might with benefit be more often used in order to minimise normal tissue sacrifice.

Basal Cell Carcinoma↗

Is routine histological evaluation an accurate test for Helicobacter pylori infection?

AIM: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C-urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago-gastro-duodenoscopy. MATERIALS AND METHODS: One-hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C-urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori-positive if two or more tests were positive. RESULTS: Eighty-one patients (70.4%) were found to be H. pylori positive. 13C-urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re-evaluation by an expert pathologist showed a high sensitivity (98. 8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%. CONCLUSION: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre-treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.

Breath Tests↗

Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.

BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.

Breast Neoplasms↗

The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only--what is the clinical significance?

BACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, with chronic reflux and Barrett's oesophagus being considered risk factors. Reliable detection of Barrett's oesophagus during upper endoscopy is therefore mandatory but requires both endoscopy and histology for confirmation. Appropriate management of patients with endoscopic suspicion but negative on histology, or vice versa, or of patients with no endoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS AND METHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50 years) referred for upper gastrointestinal endoscopy were included; 59% had reflux symptoms. The endoscopic aspect of the Z line and any suspicion of Barrett's oesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4), gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive for specialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for a final Barrett's oesophagus diagnosis. All patients with endoscopic and/or histological suspicion of Barrett's oesophagus were invited for a follow up endoscopy; the remaining cases (no endoscopic or histological suspicion of Barrett's oesophagus) were followed clinically. RESULTS: Of 235 patients positive for Barrett's oesophagus on endoscopy and/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5 months). 46% of patients with an endoscopic Barrett's oesophagus diagnosis but no histological confirmation (group A) showed the same distribution, a further 42% did not have Barrett's oesophagus, and 11% had confirmed Barrett's oesophagus on both endoscopy and biopsy on follow up. In the group with a histological Barrett's oesophagus diagnosis but negative on initial endoscopy (group B), follow up showed the same in 26% whereas 46% had no Barrett's oesophagus, and confirmed Barrett's oesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population, 16 patients had Barrett's oesophagus on initial endoscopy confirmed by histology which remained constant in 70% at follow up (group C). Of the remaining patients without an initial Barrett's oesophagus diagnosis on either endoscopy or histology (group D) and only clinical follow up (mean follow up period 38 months), one confirmed Barrett's oesophagus case was found among 100 patients re-endoscoped outside of the study protocol. However, no single case of dysplasia or cancer of the distal oesophagus was detected in any patient during the study period. CONCLUSIONS: Even in a specialised gastroenterology setting, reproducibility of presumptive endoscopic or histological diagnoses of Barrett's oesophagus at follow up were poor. Only 10-20% of cases with either endoscopic or histological suspicion of Barrett's oesophagus had established Barrett's oesophagus after 2.5 years of follow up. The risk of dysplasia in this population was very low and hence meticulous follow up may not be required.

Adolescent↗

Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage.

CONTEXT: The histologic patterns of diffuse alveolar damage (DAD), bronchiolitis obliterans with organizing pneumonia (BOOP), and eosinophilic pneumonia (EP) are well-recognized histologic patterns of lung injury associated with an acute or subacute clinical presentation. We have recognized acute fibrinous and organizing pneumonia (AFOP) as a histologic pattern, which also occurs in this clinical setting but does not meet the classic histologic criteria for DAD, BOOP, or EP and may represent an underreported variant. OBJECTIVE: To investigate the clinical significance of the AFOP histologic pattern and to explore its possible relationship to other disorders, including DAD and BOOP. DESIGN: Open lung biopsy specimens and autopsy specimens were selected from the consultation files of the Armed Forces Institute of Pathology, which showed a dominant histologic pattern of intra-alveolar fibrin and organizing pneumonia. Varying amounts of organizing pneumonia, type 2 pneumocyte hyperplasia, edema, acute and chronic inflammation, and interstitial widening were seen. Cases with histologic patterns of classic DAD, BOOP, abscess formation, or eosinophilic pneumonia were excluded. To determine the clinical behavior of patients with this histologic finding, clinical and radiographic information and follow-up information were obtained. Statistical analysis was performed using Kaplan-Meier and chi(2) analysis. RESULTS: Seventeen patients (10 men, 7 women) with a mean age of 62 years (range, 33-78 years) had acute-onset symptoms of dyspnea (11), fever (6), cough (3), and hemoptysis (2). Associations believed to be clinically related to the lung disease included definitive or probable collagen vascular disease (3), amiodarone (1), sputum culture positive for Haemophilus influenza (1), lung culture positive for Acinetobacter sp. (1), lymphoma (1), hairspray (1), construction work (1), coal mining (1), and zoological work (1). Six patients had no identifiable origin or association. Follow-up revealed 2 clinical patterns of disease progression: a fulminate illness with rapid progression to death (n = 9; mean survival, 0.1 year) and a more subacute illness, with recovery (n = 8). Histologic analysis and initial symptoms did not correlate with eventual outcome, but 5 of the 5 patients who required mechanical ventilation died (P =.007). CONCLUSIONS: Acute fibrinous and organizing pneumonia is a histologic pattern associated with a clinical picture of acute lung injury that differs from the classic histologic patterns of DAD, BOOP, or EP. Similar to these patterns of acute lung injury, the AFOP pattern can occur in an idiopathic setting or with a spectrum of clinical associations. The overall mortality rate is similar to DAD and therefore may represent a histologic variant; however, AFOP appears to have 2 distinct patterns of disease progression and outcome. The need for mechanical ventilation was the only parameter that correlated with prognosis. None of the patients with a subacute clinical course required mechanical ventilation.

Acute Disease↗

Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity.

PURPOSE: Molecular classification of gliomas is becoming increasingly important clinically as an adjunct to histopathological diagnosis. Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between histological heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas. EXPERIMENTAL DESIGN: We have used laser capture microdissection to sample the various histological phenotypes present in 42 tumors from 25 glioma cases with either inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR amplification of microsatellite markers and capillary electrophoresis to determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q. RESULTS: Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13 oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic, oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome 10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial regions present within high-grade tumors. Seven tumors from 5 cases had no detectable losses of any markers investigated. In 13 tumors with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation. Additional losses were seen in some but not all of the histologies within 2 tumors and were associated with progression in 3 cases. CONCLUSIONS: The gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated, supporting a monoclonal origin of these tumors.

Alleles↗

Focus on the histologic diversity in primary and lymph node lesions and the outcome of gastric cancer.

According to the Japanese Classification of Gastric Carcinoma, one predominant type should be selected to represent the histology of the carcinoma. The authors investigated the relationship among the histologic variables of primary lesions, metastatic lesions and the outcome of patients. A total of 155 patients with node-positive gastric carcinoma were examined. According to the histologic diversity, histologic grades were assigned from 1 to 4 regardless of the predominant histologic type. A larger number of histologic types composing not the primary lesions, but metastatic lymph nodes, were associated with an increasing frequency of advanced stage tumors. On the prognosis by number of histologic types composing the primary tumor and the metastatic lymph nodes, there were significant differences except between the histologic type-2 and histologic type-3 groups in the only metastatic lymph nodes. In conclusion, patients with a greater number of histologic types composing lymph node metastases had poorer prognosis than with a small number of histologic types. Histologic diversity within metastatic lymph node was thought to be important for determining the prognosis of patients with gastric cancer.

Adenocarcinoma↗

Impact of histology on the treatment outcome of metastatic or recurrent renal cell carcinoma.

Among 107 renal cell carcinoma (RCC) patients with histopathologic subtype diagnosis who were treated at Albert Einstein Cancer Center with cytokines over a 10-year period, seven patients had sarcomatoid histology, 63 had clear cell carcinoma, and 10 patients had mixed histology (sarcomatoid and clear cell). Regardless of their histology, patients with a disease free interval of 2 years or more had significantly better survival. None of the patients with sarcomatoid histology responded to therapy. However, several patients with mixed and clear cell histology achieved partial or complete responses following high dose Interleukin-2 (IL-2) therapy. The median survival of patients with sarcomatoid histology was the shortest (13.8 months), whilst that of patients with mixed and clear cell histology was much longer (34.8 months and 39.1 months, respectively). This result was statistically significant in both univariate and multivariate survival analysis (P < 0.001 and P < 0.01, respectively). Patients with mixed and clear cell histology had no significant difference in survival, and their median survival combined was significantly longer than that of patients with sarcomatoid histology (P < 0.0001 in univariate analysis, P < 0.01 in multivariate analysis). This study suggests that survival with a diagnosis of RCC is predicted by tumor histology and disease free interval, and this impacts on the ability to respond to standard therapy. Patients with mixed and clear cell histology respond to cytokine therapy. Other therapies should be sought for patients with sarcomatoid RCC.

Adenocarcinoma, Clear Cell↗

[Histological lesions of supraspinatus tendons in full thickness tears of the rotator cuff].

PURPOSE OF THE STUDY: Iterative tears after simple tendon bone suture of transfixiant ruptures of the rotator cuff are frequent. The frequency of iterative ruptures had seemed to be correlated to the importance of the preoperative fatty degenerations of the cuff muscles. But fatty degeneration cannot account for iterative ruptures occurring with no or little preoperative muscle fatty degeneration. The authors have tried to know if iterative ruptures could also be accounted for by the presence on repaired tendinous stumps of histological lesions which are known to lower their mechanical quality, and if such was the case, they have tried to know what could be the impact of these lesions on the repairing technique by suturing cuff ruptures. MATERIAL AND METHOD: Thirty-two distal stumps of ruptured supraspinatus, resected on more than 1 cm to eliminate macroscopic tendinous lesions (thin, lacerated, cleaved, hardened or whitish tendons) and to reach a new stump, slightly bleeding and thick enough to hold the stitches correctly, have been studied on longitudinal histological slides. RESULTS: All the tendinous resected stumps had histological anomalies: dilacerations lesions of the conjunctive tissue, fatty infiltrations, necrosis, scar lesions and micro calcifications were found. The histological lesions were often associated. The histological lesions were an average 4 mm shorter than those of the tendinous resection. In 18 cases however the whole of the resected tendon was histologically abnormal. DISCUSSION: Tendinous histological lesions found on the whole or almost the whole length of the macroscopically abnormal tendinous stumps diminish the mechanical quality of the tendons. Insufficient resection of the tendinous stumps leaving macroscopical lesions and therefore histological lesions could account for iterative ruptures in the first post operative year. Yet complete resection of the macroscopically abnormal tendinous stump does not entail that the neo tendinous stump to be repaired is histologically normal. This encourages to put the stitches well within the zone of the tendinous resection and to bury the tendinous stumps into a highly vascular bony trough. But tendinous resection although logical from the histological and mechanical point of view widens the rupture of the cuff to be repaired. It can make sutures under tension, which can entail iterative ruptures. Musculo-tendinoplasty appears then necessary to perform sutures without tension. CONCLUSION: Histological lesions of tendinous stumps of cuff ruptures correspond roughly to tendinous macroscopic lesions. They could be at the origin of iterative ruptures that take place after simple tendon-bone sutures of ruptured cuffs which are not accounted for by muscular fatty degeneration. They could also partly account for iterative ruptures taking place when pre operative fatty degeneration is evident. It seems logical to resect macroscopically abnormal tendinous stumps before performing a suture. But the tendon-bone suture without tension is then often possible only with musculo-tendinoplasties.

Aged↗

Histologic prognostication in soft tissue sarcomas: grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines.

Despite the validation of many histologic grading systems for soft tissue sarcomas, none have been universally accepted. Because of the overall rarity of specific histologic sarcoma subtypes, evaluation of grading systems and their prognostic significance have tended to base the results on sarcomas as a general group, diminishing the value and significance of histologic subtyping. A representative review of the literature regarding histologic grading of soft tissue sarcomas and its relationship to histologic subtype, stage, and prognosis is analyzed and discussed. Histologic grading of many soft tissue sarcomas appears to be a valuable predictor of patient survival, as confirmed by the literature. However, accurate histologic subtyping is essential for accurate histologic grading. Histologic grading in some sarcoma subtypes is probably not applicable and may underestimate biologic behavior. Clinicians and pathologists should be aware of the limitations, prognostic significances, and relationships of histologic subtyping and histologic grading in the therapeutic management and prognostication of soft tissue sarcomas.

Humans↗

Central zone histology of the prostate: a mimicker of high-grade prostatic intraepithelial neoplasia.

The central zone (CZ) is located at the base of the prostate adjacent to the seminal vesicles. Its histology as a potential mimicker of high-grade prostatic intraepithelial neoplasia (PIN) has not been formally studied. Three groups were evaluated. Group 1 comprised 30 consecutive radical prostatectomy specimens assessed for the extent of CZ and of Roman arch and/or cribriform formation in the CZ. Group 2 comprised 100 consecutive cases of nonconsult prostate needle biopsies, screened in a random blinded fashion to identify CZ histology and the specificity of its identification on biopsy. Group 3 comprised 34 consult cases (1984 to the present) with CZ histology on needle biopsy. For group 1, the average maximum diameter of CZ histology was 5 mm. Two cases (6.7%) did not contain the classic features of CZ histology. The average amount of cribriform and/or Roman arch formation in the areas with CZ histology was 16.5%. In group 2, 10% of prostate needle biopsy cases had CZ histology. Of these, 80% were located on biopsy specimens designated as the base of the prostate, 10% were located in the base and midportion of the prostate, and 10% were located in the midportion of the prostate. For group 3, CZ histology occupied on average 32% of the involved core. The 2 most common histologic features were eosinophilic cytoplasm (97%) and location at the end of a core (97%). Other features were Roman arch formation (59%), a prominent basal cell layer (32%), cribriform formation (26%), and associated thick muscle bundles typical of bladder neck (24%). On average, cribriform and/or Roman arch formation occupied 22% of the CZ area seen on biopsy. Twenty-six of the consult cases were sent in with preliminary outside diagnoses. Of these, 21 (81%) were either PIN or atypical: 11 (42%) high-grade PIN, 7 (27%) PIN, and 3 (12%) atypical glands. Our findings show that CZ histology is distinctive, as seen in radical prostatectomy specimens. Less frequently it is found on needle biopsy, where the presence of Roman arch and/or cribriform formation mimics PIN. Recognition of the distinctive features of CZ histology (i.e., tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer, and lack of cytologic atypia) can help avoid a misdiagnosis of PIN or "atypia" on needle biopsy.

Biopsy, Needle↗