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PubMed2003

Seizure outcome after temporal lobectomy in temporal lobe cortical dysplasia.

PURPOSE: To identify the temporal lobe cortical dysplasia (CD) histopathology classification subtype and determine the seizure outcome of patients who underwent temporal lobectomy with coincident CD. METHODS: We reviewed the data of 28 patients with temporal lobe epilepsy who underwent surgery with pathologically verified CD at our institution from 1990 to 2000. The seizure outcome was assessed at a minimum of 1 year after surgery according to Engel's classification. RESULTS: Of 28 patients who underwent surgery, nine (32.1%) had isolated CD, and 19 (67.9%) had CD and hippocampal sclerosis (CD&HS). Twenty-six (92.9%) patients had histopathology subtype Ia (architectural abnormalities). Twenty (71.4%) patients were seizure free (Engel class I). Favorable seizure outcome (Engel class I, II) was achieved in 26 (92.9%) patients. No difference in seizure outcome was noted between patients with CD and CD&HS. CONCLUSIONS: The most common histopathologic subtype in patients with temporal lobe CD is type Ia (architectural abnormalities). Temporal lobectomy in temporal lobe epilepsy patients with CD can achieve favorable seizure outcome.

Adolescent↗
PubMed1999

[Pathology of childhood and adolescent rhabdomyosarcoma].

Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence. The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called 'International Classification of Rhabdomyosarcoma' includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.

Adolescent↗
PubMed1990

Amyloid deposits in basal cell carcinoma of the skin. A pathologic study of 199 cases.

Deposits of amyloid were detected in 101 of 199 basal cell carcinomas (51%). The frequency of amyloid deposits in solid, adenoid, and cystic histologic subtypes was slightly higher than overall, whereas in partial sclerosing and morphea-like tumors the frequency was much lower. The amyloid of basal cell carcinoma showed histochemical characteristics that were different from those of locally deposited amyloid in endocrine tumors such as medullary carcinoma thyroid and from those of "secondary" amyloid. No major differences in the histochemical characteristics, however, were observed between amyloid associated with basal cell carcinoma and myeloma-associated or "primary" amyloid. Nevertheless, immunohistochemical staining with rabbit antihuman keratin antibodies by the peroxidase antiperoxidase technique demonstrated positivity only in amyloid deposits associated with basal cell carcinoma and not in those of myeloma-associated amyloid. This evidence supports the concept that amyloid of basal cell carcinoma is produced in the stroma from degenerated epithelial cells through filamentous degeneration or apoptosis.

Amyloid↗
PubMed1982

Changing patterns of Hodgkin's disease at autopsy: a 25-year experience at the National Cancer Institute, 1953--1978.

The pathologic findings at autopsy in 124 patients with an initial diagnosis of Hodgkin's disease (HD) were evaluated to assess the effects of treatment on the anatomic extent and histologic appearance of residual HD. Further, the effects of duration of disease, vascular invasion, and histologic subtype at diagnosis on sites of involvement were considered. The 124 autopsied cases came from a cohort of 345 patients admitted for treatment at the National Cancer Institute between 1953 and 1969, with followup extended to 1978. The pathologic review included extensive organ sampling; greater than 12,000 slides were reviewed. The study period spans 25 years, ranging from a period of palliative therapy (81 cases, pre-1965) to the modern curative treatment era (43 cases, 1965 or later). A distinct reduction in the extent of disease at autopsy was noted in the group treated with curative intent. Reduced involvement was the rule for most, but not all, organ sites, with the reduction greater for certain histologic types. Some organs had a comparable incidence of involvement with early and late deaths. Histologic assessment identified an atypical monomorphic form of residual HD (treatment-altered HD) in patients from both treatment eras but most consistently in the post-1965 group. Vascular invasion occurred in 43% of cases. The incidence of extranodal involvement was considerably higher in patients with vascular invasion, indicating that vascular spread is a factor in extranodal spread and in lethal cases of HD.

Adult↗
PubMed1991

Histopathologic features of high-grade non-Hodgkin's lymphomas in acquired immunodeficiency syndrome. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors.

High-grade B-cell non-Hodgkin's lymphomas are observed in 5% to 10% of patients with acquired immunodeficiency syndrome. To describe their histologic subtypes, a group of pathologists was formed. One hundred thirteen cases were reviewed and classified according to the Working Formulation, the updated Kiel classification, and a recent description of morphologic variants of high-grade B-cell non-Hodgkin's lymphoma. Three major types of intermediate- or high-grade lymphomas were observed: (1) large-cell or centroblastic mainly polymorphic lymphomas with a component of immunoblasts (35 cases); (2) immunoblastic lymphomas with plasmablastic and plasmacytic features in most cases (33 cases); and (3) small non-cleaved cell Burkitt's or non-Burkitt's lymphoma (41 cases), with 15 cases fitting typical criteria of Burkitt's lymphoma and 26 heterogeneous cases in which the size and shape of the cells and the presence of plasmablastic features varied. The most frequent pathologic sites of involvement at presentation were the lymph nodes, gastrointestinal tract, bone marrow, brain, oral cavity, and muscles. A comparison between the histologic type and the site of involvement showed that most cases involving lymph nodes, bone marrow, or muscles were small noncleaved cell Burkitt's or non-Burkitt's lymphomas, while those that affected the gastrointestinal tract, brain, and oral cavity were centroblastic or immunoblastic lymphomas with consistent plasmacytic differentiation. In 10 cases, previous persistent generalized lymphadenopathy syndrome was present. In 13 cases, the lymphomatous proliferation was associated with follicular or diffuse hyperplasia seen on the same lymph node biopsy specimen or in another lymph node.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Prognostic Factors in Hodgkin's Disease.

Prognostic factors in Hodgkin's disease (HD) are reviewed. The Ann Arbor staging classification remains the basis for evaluation of patients with HD. However, subgroups of patients with differing prognoses exist within the individual stages. In pathological stages I and II, the number of involved regions and the tumor mass in each region are important, and an estimate of the total tumor burden has proved significant. B symptoms, histological subtype, age, and gender are also generally significant but less important. Prognostic factors for laparotomy findings in clinical stages I and II are: number of involved regions, disease confined to upper cervical nodes, B symptoms, gender, histology, age, and mediastinal disease (variable influence). In clinical stages I and II, the same prognostic factors apply as for pathological stages I and II and for laparotomy findings, and also some indirect indicators of extent of disease such as erythrocyte sedimentation rate, anemia, and serum albumin. In advanced disease the number of involved nodal and extranodal regions, the total tumor burden, B symptoms, age, gender, histology, and a number of hematologic and biochemical indicators are significant. Research into serum values of certain HD-associated antigens and cytokines may in the future provide valuable tumor markers in HD.

Journal Article↗
PubMed2000

Angiotensin II AT2 subtype receptors: an emerging target for cardiovascular therapy.

This article reviews the impressive amount of knowledge accumulated in the last few years on the angiotensin II AT2 subtype receptor. Although still elusive, a large body of experimental evidence strongly suggests that it may play an important role in the adaptive changes of the cardiovascular structures in response to pathological conditions such as myocardial infarction, congestive heart failure or hypertension. The most intriguing aspects of the biology of this receptor, however, appear to be: 1) the regulation of its transcription, which plays an important role in the expression of the protein in adults or in injured tissues; 2) its interaction or "cross-talk" with the predominant angiotensin II receptor, the AT1 subtype, or with the receptors of other growth factors or cytokines; and 3) its connections with the bradykinin/nitric oxide pathways. These aspects may be relevant for the therapeutical use of drugs which antagonize the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, as well as for new therapeutic approaches to the treatment of cardiovascular diseases.

Angiotensin II↗
PubMed2006

Prognosis of patients with resected non-small cell lung cancer: impact of clinical and pathologic variables.

The objective of this study was to determine whether AJCC staging, supplemented by additional clinical and pathologic variables could identify a subpopulation of pathologically staged NSCLC patients who had been resected for cure with a low risk (<20%) of 5-year disease specific mortality. The Surveillance, Epidemiology, and End Results (SEER) registry was analyzed to identify and evaluate the disease specific 5-year mortality of 17,130 patients with resected and pathologically defined Stage I-IIIA disease initially diagnosed from 1988 to 1997. The analyses showed that American Joint Commission on Cancer (AJCC) T and N defined stage Stage I-IIIA subgroups had approximately a 30, 60, and 75% 5-year disease specific mortality, respectively. The 5,366 Stage IA patients were identified as having a 5-year disease specific mortality of 25%. Further multivariate analyses of Stage IA cases showed predictors of favorable outcome to be tumor size (< 10 mm), histologic grade (well differentiated), and histologic subtype (bronchoalveolar cell). Subgroups identified with two or all three of these additional features had an approximately 10% 5-year lung cancer specific mortality. Although nearly all patient subgroups with Stages I-IIIA resected and pathologically staged NSCLC have substantial (>20%) risk of death from their cancer within 5 years of diagnosis, for Stage IA patients additional information (tumor size, histologic grade, and histologic subtype) allows additional refinement in prognostic estimates and identification of some low risk subgroups.

Adult↗
PubMed2002

Incidence and case fatality rates of stroke subtypes in a multiethnic population: the South London Stroke Register.

OBJECTIVE: To identify sociodemographic differences in the incidence of the subtypes of first ever stroke in a multiethnic population. METHODS: A prospective community stroke register (1995-8) was developed using multiple notification sources and pathological and clinical classifications of stroke. Standardisation of rates was to European and World populations and adjusted for age, sex and socioeconomic status in multivariate analyses. A multiethnic population of 234 533 in south London, of whom 21% are black was studied. RESULTS: A total of 1254 cases were registered. The average age of stroke was 71.7 years with black patients being 11.3 years younger than white patients (p<0.0001). The incidence rate/1000 population was 1.33 (crude) (95% CI 1.26 to 1.41), 1.28 (European adjusted) (95% CI 1.2 to 1.35) with a 2.18 (95% CI 1.86 to 2.56) (p<0.0001) age and sex adjusted incidence rate ratio in the black population. Radiological diagnosis was confirmatory in 1107 (88.3%) with 862 (68.7%) infarction, 168 (13.4%) primary intracerebral haemorrhage, and 77 (6.2%) subarachnoid haemorrhage. Of the cerebral infarction cases 189 (21.9%) were total anterior circulatory, 250 (29%) partial anterior, 141 (16.4%) posterior (POCI) and 282 (32.7%) lacunar infarcts. The black group had a significantly higher incidence of all subtypes of stroke except for POCI and unclassified strokes. The incidence rate ratio (IRR) for men compared with women was 1.34 (95% confidence interval (95% CI) 1.19 to 1.50; p<0.001). The IRR for manual versus non-manual occupations in those aged 35-64 years was 1.64 (95%CI 1.22 to 2.23; p<0.0001). There was a borderline significant increase in adjusted survival at 6 months in the black group 95% (CI 0.61 to 1.03, p=0.078) with a hazard ratio of 0.79 after adjustment and stratification. CONCLUSIONS: Although the black population is at increased risk of stroke and most subtypes of stroke, this is not translated into significant differences in survival. Hence black/white differences in mortality are mainly driven by incidence of stroke. There are striking demographic inequalities in the risk of stroke in this multiethnic inner city population that need to be tackled through interagency working. Although the reasons for the increased risk in the black population are unclear, demographic factors such as socioeconomic status do seem to play a significant independent part.

Adolescent↗
PubMed2001

Unusual T- and T/NK- cell non-Hodgkin's lymphoma of the larynx: a diagnostic challenge for clinicians and pathologists.

BACKGROUND: Lymphomas of T-cell and T/natural killer (T/NK)-cell types rarely involve the larynx. Early symptoms are subtle and nonspecific, and confirmation of the diagnosis is often difficult. Because of the rarity of this disease entity, the optimal management remains controversial. METHODS: The case records of patients with the diagnosis of lymphoma involving the larynx were retrospectively reviewed. Details of the pathologic condition, the difficulties in diagnosis, and treatment were presented. RESULTS: One case of T-cell lymphoma (Lennert's lymphoma subtype) and two cases of T/NK-cell lymphomas involving the larynx were presented. The diagnoses were all difficult to establish. All three patients received either multiagent chemotherapy or radiotherapy as the first-line treatment. They all died of the disease within 32 months of diagnosis. CONCLUSIONS: T- and T/NK-cell non-Hodgkin's lymphoma of the larynx is a diagnostic challenge for clinicians and pathologists. Conventional chemotherapy or radiotherapy has not been effective. A more aggressive therapy should be considered.

Adult↗
PubMed2002

Evaluation of relationship between chromosome 22 and p53 gene alterations and the subtype of meningiomas by the interphase-FISH technique.

In this study, we investigated the relationship between genetic alterations such as chromosome 22 aneuploidy and p53 gene deletion, and the pathological types of meningioma of typical and aggressive forms. Thirty-four meningiomas (23 typical and 11 aggressive) were examined by application of fluorescence in situ hybridization (FISH) with chromosome 22 specific alpha satellite probe and a combination of p53 locus specific and chromosome 17 centromere specific alpha satellite probes, to evaluate the chromosome 22 aneuploidy and gain or loss of p53 gene along with chromosome 17. The results showed that, although chromosome 22 aneuploidy was seen in 7 out of 23 typical (30.4%) and 4 out of 11 aggressive meningiomas (36.3%), no p53 deletion was detected in typical meningiomas, and p53 deletion was detected in 3 out of 11 aggressive meningiomas (1 atypical and 2 malignant), which had recurrence. There were no simultaneous occurrences of p53 gene deletions between typical and aggressive meningiomas. The present findings indicate that the loss of chromosome 22 may be involved with tumorogenesis of typical and aggressive meningiomas, while p53 gene deletions may be involved with malignant progression and recurrence in the aggressive meningiomas.

Adult↗
PubMed1988

Congenital nystagmus: a clinical perspective in infancy.

In a series of 152 patients with congenital nystagmus, 119 had sensory nystagmus while 13 had pure motor nystagmus. The most common diagnoses in the sensory group were optic nerve hypoplasia. Leber's amaurosis, and oculocutaneous or ocular albinism. Eight of the patients in the motor group had a similarly afflicted parent. Diagnostic features in infants and preverbal children were reviewed. This study supports the continued clinical classification of congenital nystagmus into sensory and motor subtypes.

Albinism↗
PubMed2006

The influence of additional surgical margins on the total specimen volume excised and the reoperative rate after breast-conserving surgery.

BACKGROUND: It is unclear whether the additional removal of breast tissue during breast-conserving therapy (BCT) for breast cancer beyond the standard lumpectomy reduces the incidence of inadequate microscopic margins found at pathological examination and subsequent reoperation. This study compares the reoperative rates after initial BCT in 3 groups of patients who underwent lumpectomy with complete resection of 4 to 6 additional margins, lumpectomy with selective resection of 1 to 3 additional margins, or standard lumpectomy. METHODS: Retrospective data were reviewed from 171 selected cases of BCT, from May 2000 to February 2006. Forty-five cases involved lumpectomy with complete resection of 4 to 6 additional margins; 77 involved lumpectomy with selective resection of 1 to 3 additional margins, whereas 49 involved standard lumpectomy. All samples underwent pathologic analysis of inked resection margins by permanent section. The 3 groups were compared for patient demographics, tumor size and histologic subtype, tumor stage, margin status, excised specimen volume, and eventual subsequent reoperation. Adequate surgical margin was defined as any negative margin greater than 2 mm. RESULTS: The group with complete resection of 4 to 6 additional margins had a subsequent reoperation rate of 17.7%, whereas the group with selective resection of 1 to 3 additional margins and the standard lumpectomy group had a subsequent reoperation rate of 32.5% and 38.7%, respectively, because of inadequate margins. The mean total excised specimen volume in the 3 groups was 129.19, 46.04, and 37.44 cm3, respectively. CONCLUSIONS: The complete resection of 4 to 6 additional margins during the initial BCT resulted in the lowest subsequent reoperation rate, and the largest total volume specimen excised among the 3 techniques studied.

Adult↗
PubMed1999

The role of microglia and macrophages in the pathophysiology of the CNS.

Microglia are a major ghal component of the central nervous system (CNS) and are extremely sessile. Only a subtype, the perivascular microglia, are regularly replaced from the bone marrow in adult animals. Microglia respond to virtually any, even minor pathological events in the CNS. In most pathological settings microglia are aided by infiltrating hematogenous macrophages. Upon activation microglia and macrophages share most phenotypical markers and can exert similar effector functions. After transection of a CNS fibre tract microglia are insufficiently activated and hematogenous macrophages do not significantly enter the degenerating nerve stump. Thereby myelin debris that contains neurite outgrowth inhibiting activity persists for long time. This is in sharp contrast to the peripheral nervous system in which hematogenous macrophages are rapidly recruited in response to axotomy and clear myelin debris allowing regrowth of axons from the proximal stump. However, CNS lesion paradigms with breakdown of the blood-brain barrier such as cerebral ischemia, brain abscesses and stab wounds elicit prompt microglial activation, macrophage recruitment and debris clearance. There is increasing evidence that microglia play an active part in degenerative CNS diseases. In Alzheimer's disease activated microglia appear to be involved in plaque formation. In experimental globoid cell dystrophy T-cell independent induction of major histocompatibility complex class II molecules on microglia accelerates demyelination. In autoimmune diseases microglia probably have dual functions. Microglia present antigen to infiltrating T cells and exert effector functions thereby locally augmenting immune responses. On the other hand, microglia have the capacity to downregulate T cell responses. In the human acquired immunodeficiency syndrome (AIDS) virus infected macrophages probably introduce the virus to the CNS and in concert with microglia are involved in the pathophysiology of the AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗
PubMed2001

NMDA receptor subunits: diversity, development and disease.

N-methyl-D-aspartate receptors (NMDARs) are present at many excitatory glutamate synapses in the central nervous system and display unique properties that depend on their subunit composition. Biophysical, pharmacological and molecular methods have been used to determine the key features conferred by the various NMDAR subunits, and have helped to establish which NMDAR subtypes are present at particular synapses. Recent studies are beginning to address the functional significance of NMDAR diversity under normal and pathological conditions.

Alternative Splicing↗
PubMed2002

Cutaneous lymphomas: which pathological classification?

Cutaneous lymphomas are rare and although some are a manifestation of systemic lymphoma, the majority arise primarily from the skin. These primary cutaneous lymphomas comprise predominantly T cell subtypes and represent a wide spectrum of disorders. Pathologists can currently choose to label these conditions according to three classifications (REAL, EORTC or WHO) but each has shortcomings. Nonetheless, in an attempt to unify the field, we would recommend that pathologists make every attempt to categorise these conditions according to the WHO classification. This classification can encompass all the conditions and aligns the cutaneous lymphomas with the broader systemic lymphoproliferative conditions.

Adult↗
PubMed2005

Localization of endothelin-converting enzyme in bovine optic nerve and retina.

A significant loss and remodeling of the lamina cribrosa tissue leading to the excavation of the optic nerve is seen in glaucoma. Elevated endothelin-1 (ET-1) levels are detected in the aqueous humor of patients of open-angle glaucoma and in the plasma of patients with normal- tension glaucoma. Optic nerve damage, including axonal loss, can be mimicked by ET-1 injection near the optic nerve. ET-1 is produced from its precursor Big ET-1 (38 amino acids) by endothelin-converting enzyme (ECE). Although ET-1 and its receptors have been identified in the retina, little is known of the distribution of ECE at the optic nerve. Presently, ET-1 receptors and Big ET-1 converting activities were characterized in bovine optic nerve and the retina. The ET(B) receptor was detected in both the optic nerve and retina by immunoblotting and cross-linking, using 125I-ET-1. However, the ET(A) receptor was detected only in the retina. Big ET-1 conversion activities were detected in the plasma membrane (PM) of bovine retina, but not in the PM of the optic nerve. The retinal PM Big ET-1 converting activity was inhibited by phosphoramidon, thiorphan, and acidification. Furthermore, ECE cytosolic activities were detected in both the optic nerve and retina. Unlike the PM-ECE, cytosolic Big ET-1 converting activities were activated by acidification (pH 6.4), suggesting the involvement of ECE-2-like activity and/or cathepsin activity. Pepstatin, a potent inhibitor of cathepsins, inhibited the optic nerve (ON) cytosolic conversion of Big ET-1 peptide by 50%, and the combination of pepstatin and phosphoramidon, a potent inhibitor of ECE, inhibited the ON cytosolic activity by 86%. By contrast, the combination of both inhibitors weakly inhibited the cytosolic retinal Big ET-1 converting activity. Western blotting revealed the presence of ECE-1 at the PM of the retina not the ON. ECE-2 and cathpesins B, D, and L were detected only in the cytosol of both the retina and ON. In summary, it appears that ET-1 could be produced in the retina and optic nerve by at least two ECE subtypes and, perhaps, cathepsins. Big ET-1 converting activity may be an important target in preventing ET-1-induced optic nerve pathology.

Animals↗